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Dental Stem Cells Research

Published Medical Research

07/30/2018 - Dental follicle mesenchymal stem cells down-regulate Th2-mediated immune response in asthmatic patients mononuclear cells

Abstract

Asthma is a chronic inflammatory disease in which inflammatory responses have the polarisation of CD4+ T cells to Th2 cellsDental follicle mesenchymal stem cells (DFSCs) have strong anti-inflammatory properties comparable to other mesenchymal stem cells.

We investigated the immunomodulatory effects of DFSCs on CD4+ T helper cell responses of asthmatic patients and compared the results with those obtained with asthmatic subjects on immunotherapy and with healthy individuals.

Conclusion: Dental follicle mesenchymal stem cells suppressed allergen-induced Th2-cell polarisation in favour of Th1 responses and attenuated antigen-presenting cell co-stimulatory activities. These studies suggest that DFSC-based cell therapy may provide pro-tolerogenic immunomodulation relevant to allergic diseases such as asthma.

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07/26/2018 - Origin and Clinical Applications of Neural Crest-Derived Dental Stem Cells

Abstract

Over the past few decades, scientific research into neural crest-derived stem cells has progressed rapidly. The migration and differentiation of neural crest-derived stem cells has been an interesting area of research. Stem cells within teeth originating from the embryonic neural crest have attracted increasing attention in clinical and scientific research because they are easy to obtain and have superb stemness. The stem cells within the teeth include dental pulp stem cells (DPSCs), dental follicle stem cells (DFSCs), stem cells from apical papilla (SCAPs), stem cells from human exfoliated deciduous teeth (SHEDs), and periodontal ligament stem cells (PDLSCs). To date, there have been several interesting studies focusing on dental pulp regeneration, neural regeneration and the revascularization for therapeutic applications.

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07/25/2018 - Dental stem cells as a cell source for tissue engineering
Abstract
Dental stem cells (DSCs) have been isolated from dental follicles, pulps, root apical papillae, and periodontal ligaments of extracted teeth, and all have exhibited multipotential, self-renewal, and mesenchymal stem cell (MSC) characteristics,. However, DSCs from different sources vary in their differentiation properties: stem cells from dental follicles or root apical papillae of wisdom teeth showed superior osteogenic differentiation potential, whereas dental pulp stem cells demonstrated remarkably enhanced in vitro and in vivo neurogenic differentiation ability,,. Importantly, a new tissue cryopreservation protocol has developed for use as an autologous stem cell source. In previous reports, MSCs were successfully isolated from long-term cryopreserved dental tissues (follicles, pulps, and root apical papillae),. MSCs from cryopreserved dental tissues showed identical characteristics to those from fresh dental tissues, including stemness, in vitro differentiation potential, and cell proliferation rate,. This tissue cryopreservation method makes it possible to safely store dental tissues after tooth extraction for a long time, allowing them to be used as an autologous stem cell resource. Cells from autologous source may reduce unexpected side effects, such as various immune reactions, when they were in vivo transplanted.
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07/24/2018 - Dental stem cell and dental tissue regeneration

Abstract

The teeth are highly differentiated chewing organs formed by the development of tooth germ tissue located in the jaw and consist of the enamel, dentin, cementum, pulp, and periodontal tissue. Moreover, the teeth have a complicated regulatory mechanism, special histologic origin, diverse structure, and important function in mastication, articulation, and aesthetics. These characteristics, to a certain extent, greatly complicate the research in tooth regeneration. Recently, new ideas for tooth and tissue regeneration have begun to appear with rapid developments in the theories and technologies in tissue engineering. Numerous types of stem cells have been isolated from dental tissue, such as dental pulp stem cells (DPSCs), stem cells isolated from human pulp of exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), stem cells from apical papilla (SCAPs), and dental follicle cells (DFCs). All these cells can regenerate the tissue of tooth. 

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07/24/2018 - Regeneration of insulin-producing islets from dental pulp stem cells using a 3D culture system

Abstract

In this study, we aimed to establish the differentiation protocol of dental pulp stem cells (DPSCs) into pancreatic islets using a 3D structure.

Islet formation increased insulin and C-peptide production, and enhanced the expression of pancreatic markers. Glucose-dependent secretion of insulin was increased by islets. Pancreatic endocrine markers, transcriptional factors, and the PI3K/AKT and WNT pathways were also upregulated.

Pancreatic islets were generated from DPSCs in a 3D culture system. This system could provide novel strategies for controlling diabetes through regenerative medicine.

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07/24/2018 - Cryopreservation of Dental Stem Cells

Abstract

Nowadays, regenerative and reparative medicine has grown in popularity. Dental stem cells are easily accessible source of adult stem cells. They can be harvested by a tooth extraction or spontaneous deciduous tooth exfoliation. They have to be isolated, expanded and stored until time they would be needed for individual stem cell therapy. Cryopreservation is both a short-term and long-term storage of tissues or cells at sub-zero temperatures. There are several methods of cryopreservation requiring different technologies. The objective of this review is to compare them and highlight their advantages and disadvantages.

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07/23/2018 - A Bilayered Scaffold Provides Differential Cues for the Differentiation of Dental Pulp Stem Cells

Abstract

Regenerative Endodontics (RE) is a clinical procedure that aims to regenerate the dentin-pulp complex (DPC) inside the root canal. Current clinical outcomes of RE are unpredictable, and the regenerated tissue lacks the spatial organization seen in normal DPC. The purpose of this study was to develop and characterize in vitro a bilayered scaffold with distinct porosities on each side that supports differential penetration and odontoblastic differentiation of cultured human dental pulp stem cells (DPSCs).

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07/23/2018 - Dental Pulp Stem Cell-Derived, Scaffold-Free Constructs for Bone Regeneration

Abstract

In the present study, a scaffold-free tissue construct was developed as an approach for the regeneration of tissue defects, which produced good outcomes. We fabricated a scaffold-free tissue construct from human dental pulp stem cells (hDPSCs construct), and examined the characteristics of the construct. For its fabrication, basal sheets prepared by 4-week hDPSCs culturing were subjected to 1-week three-dimensional culture, with or without osteogenic induction, whereas hDPSC sheets (control) were fabricated by 1-week culturing of basal sheets on monolayer culture. The hDPSC constructs formed a spherical structure and calcified matrix that are absent in the control. The expression levels for bone-related genes in the hDPSC constructs were significantly upregulated compared with those in the control. Moreover, the hDPSC constructs with osteogenic induction had a higher degree of calcified matrix formation, and higher expression levels for bone-related genes, than those for the hDPSC constructs without osteogenic induction. These results suggest that the hDPSC constructs with osteogenic induction are composed of cells and extracellular and calcified matrices, and that they can be a possible scaffold-free material for bone regeneration.

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07/20/2018 - Potential Roles of Dental Pulp Stem Cells in Neural Regeneration and Repair

Abstract

This review summarizes current advances in dental pulp stem cells (DPSCs) and their potential applications in the nervous diseases. Injured adult mammalian nervous system has a limited regenerative capacity due to an insufficient pool of precursor cells in both central and peripheral nervous systems. Nerve growth is also constrained by inhibitory factors (associated with central myelin) and barrier tissues (glial scarring). Stem cells, possessing the capacity of self-renewal and multicellular differentiation, promise new therapeutic strategies for overcoming these impediments to neural regeneration. Dental pulp stem cells (DPSCs) derive from a cranial neural crest lineage, retain a remarkable potential for neuronal differentiation, and additionally express multiple factors that are suitable for neuronal and axonal regeneration. DPSCs can also express immunomodulatory factors that stimulate formation of blood vessels and enhance regeneration and repair of injured nerve. These unique properties together with their ready accessibility make DPSCs an attractive cell source for tissue engineering in injured and diseased nervous systems. In this review, we interrogate the neuronal differentiation potential as well as the neuroprotective, neurotrophic, angiogenic, and immunomodulatory properties of DPSCs and its application in the injured nervous system. Taken together, DPSCs are an ideal stem cell resource for therapeutic approaches to neural repair and regeneration in nerve diseases.

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07/19/2018 - Allogeneic transplantation of mobilized dental pulp stem cells with the mismatched dog leukocyte antigen type is safe and efficacious for total pulp regeneration

Abstract

We recently demonstrated that autologous transplantation of mobilized dental pulp stem cells (MDPSCs) was a safe and efficacious potential therapy for total pulp regeneration in a clinical study. The autologous MDPSCs, however, have some limitations to overcome, such as limited availability of discarded teeth from older patients. In the present study, we investigated whether MDPSCs can be used for allogeneic applications to expand their therapeutic use.

Analysis of dog leukocyte antigen (DLA) was performed using polymerase chain reaction from blood. Canine allogeneic MDPSCs with the matched and mismatched DLA were transplanted with granulocyte-colony stimulating factor in collagen into pulpectomized teeth respectively (n?=?7, each). Results were evaluated by hematoxylin and eosin staining, Masson trichrome staining, PGP9.5 immunostaining, and BS-1 lectin immunostaining performed 12 weeks after transplantation. The MDPSCs of the same DLA used in the first transplantation were further transplanted into another pulpectomized tooth and evaluated 12 weeks after transplantation.

There was no evidence of toxicity or adverse events of the allogeneic transplantation of the MDPSCs with the mismatched DLA. No adverse event of dual transplantation of the MDPSCs with the matched and mismatched DLA was observed. Regenerated pulp tissues including neovascularization and neuronal extension were quantitatively and qualitatively similar at 12 weeks in both matched and mismatched DLA transplants. Regenerated pulp tissue was similarly observed in the dual transplantation as in the single transplantation of MDPSCs both with the matched and mismatched DLA.

Dual allogeneic transplantation of MDPSCs with the mismatched DLA is a safe and efficacious method for total pulp regeneration.

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07/18/2018 - Dental Stem Cells Harvested from Third Molars Combined with Bioactive Glass Can Induce Signs of Bone Formation In Vitro

Abstract

The aim of this study was to assess the interaction of a bioactive glass scaffold with cells derived from dental pulp, dentalfollicle and periodontal ligament.

Impacted third molars were surgically removed from three young donors. Cells from the dental pulp, follicle and periodontal ligament tissues were isolated and expanded. Different cell populations were characterised using specific CD markers. Expanded pulp, follicle and periodontal cells were then seeded onto bioactive glass scaffolds and cultured in osteogenic medium or basic medium. Cell attachment, viability, proliferation and alkaline phosphatase activity were assessed.

This study revealed good biocompatibility of the specific bioactive glass configuration tested and the osteogenic induction of cellsderived from dental pulp, dental follicle and periodontal ligament. Osteogenic medium seemed to increase the differentiation pattern and dental pulp stem cells showed the most positive results compared to periodontal ligament and dental follicle stem cells.

Dental pulp stem cells combined with a bioactive glass scaffold and exposed to osteogenic medium in vitro represent a promising combination for future study of hard tissue regeneration in the cranio-maxillofacial skeleton.

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07/17/2018 - Therapeutic effect of dental pulp stem cell transplantation on a rat model of radioactivity-induced esophageal injury

Abstract

Dental pulp stem cell (DPSC) transplantation has been demonstrated to promote the regeneration and repair of tissues and organs and is a potentially effective treatment for radioactive esophageal injury. In this study, to explore the therapeutic effects of DPSCs on acute radiation-induced esophageal injury, DPSCs were cultured and transplanted into rats with acute radioactive esophageal injuries induced by radioactive 125I seeds in vivo. In the injured esophagus, PKH26-labeled DPSCs co-localized with PCNA, CK14, CD71, and integrin a6, and the expression levels of these four makers of esophageal stem cells were significantly increased. After DPSC transplantation, the injured esophagus exhibited a greater thickness. In addition, the esophageal function and inflammation recovered faster. The results demonstrated that transplanted DPSCs, which trans-differentiated into esophageal stem cells in vivo, could repair the damaged esophageal tissue.

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07/16/2018 - Development of a Novel Large Animal Model to Evaluate Human Dental Pulp Stem Cells for Articular Cartilage Treatment

Abstract

Chondral lesion is a pathology with high prevalence, reaching as much as 63% of general population and 36% among athletes. The ability of human Dental Pulp Stem Cells (DPSCs) to differentiate into chondroblasts in vitro suggests that this stem cell type may be useful for tissue bioengineering. However, we have yet to identify a study of large animal models in which DPSCs were used to repair articular cartilage. Therefore, this study aimed to describe a novel treatment for cartilage lesion with DPSCs on a large animal model.

Flow cytometry confirmed characterization of DPSCs as MSCs. Macroscopic and histological findings suggested that this time period was reasonable for evaluating cartilage repair. To our knowledge, this study provides the first description of an animal model using DPSCs to study the differentiation of hyaline articular cartilage in vivo.

The animals tolerated the procedure well and did not show clinical or histological rejection of the DPSCs, reinforcing the feasibility of this descriptive miniature pig model for pre-clinical studies.

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10/03/2017 - Neural crest-derived dental stem cells--where we are and where we are going

Abstract

There are five types of post-natal human dental stem cells that have been identified, isolated and characterized. Here, we review the information available on dental stem cells as well as their potential applications in dentistry, regenerative medicine and the development of other therapeutic approaches.

Dental stem cells have the capacity to differentiate into endoderm, mesoderm and ectoderm tissues. Consequently they do not only have applications in dentistry, but also neurodegenerative and ischemic diseases, diabetes research, bone repair, and other applications in the field of tissue regeneration.

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10/03/2017 - The neurotrophic effects of different human dental mesenchymal stem cells

Abstract

The current gold standard treatment for peripheral nerve injury is nerve grafting but this has disadvantages such as donor site morbidity. New techniques focus on replacing these grafts with nerve conduits enhanced with growth factors and/or various cell types such as mesenchymal stem cells (MSCs). Dental-MSCs (D-MSCs) including stem cells obtained from apical papilla (SCAP), dental pulp stem cells (DPSC), and periodontal ligament stem cells (PDLSC) are potential sources of MSCs for nerve repair. Here we present the characterization of various D-MSCs from the same human donors for peripheral nerve regeneration. SCAP, DPSC and PDLSC expressed BDNF, GDNF, NGF, NTF3, ANGPT1 and VEGFA growth factor transcripts. Conditioned media from D-MSCs enhanced neurite outgrowth in an in vitro assay. Application of neutralizing antibodies showed that brain derived neurotrophic factor plays an important mechanistic role by which the D-MSCs stimulate neurite outgrowth. SCAP, DPSC and PDLSC were used to treat a 10 mm nerve gap defect in a rat sciatic nerve injury model. All the stem cell types significantly enhanced axon regeneration after two weeks and showed neuroprotective effects on the dorsal root ganglia neurons. Overall the results suggested SCAP to be the optimal dental stem cell type for peripheral nerve repair.

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06/20/2017 - Human dental pulp stem cells: Applications in future regenerative medicine

Abstract

Stem cells are pluripotent cells, having a property of differentiating into various types of cells of human body. Several studies have developed mesenchymal stem cells (MSCs) from various human tissues, peripheral blood and body fluids. These cells are then characterized by cellular and molecular markers to understand their specific phenotypes. Dental pulp stem cells (DPSCs) are having a MSCs phenotype and they are differentiated into neuron, cardiomyocytes, chondrocytes, osteoblasts, liver cells and ß cells of islet of pancreas. Thus, DPSCs have shown great potentiality to use in regenerative medicine for treatment of various human diseases including dental related problems. These cells can also be developed into induced pluripotent stem cells by incorporation of pluripotency markers and use for regenerative therapies of various diseases. The DPSCs are derived from various dental tissues such as human exfoliated deciduous teeth, apical papilla, periodontal ligament and dental follicle tissue. This review will overview the information about isolation, cellular and molecular characterization and differentiation of DPSCs into various types of human cells and thus these cells have important applications in regenerative therapies for various diseases. This review will be most useful for postgraduate dental students as well as scientists working in the field of oral pathology and oral medicine.

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06/20/2017 - Secretome Cues Modulate the Neurogenic Potential of Bone Marrow and Dental Stem Cells.

Abstract


Dental tissue is emerging as a promising source of stem cells especially in nerve regeneration mainly due to their neural origin and ease of harvest. We isolated dental stem cells from three sources, namely, dental pulp (DPSCs), dental follicle (DFSCs), and apical papilla (SCAP), and explored the efficacy of each towards neural differentiation in comparison to bone marrow-derived stem cells. The neural differentiation potential was assessed by expression of various neural markers and neurosphere assay. We observed that DPSCs were inherently predisposed towards neural lineage. To further delineate the paracrine cues responsible for the differences in neural differentiation potential, we harvested the conditioned secretome from each of the stem cell population and observed their effect on colony formation, neurite extension, and neural gene expression of IMR-32, a pre-neuroblastic cell line. We found that neural differentiation was significantly enhanced when IMR-32 cells were treated with secretome derived from DMSCs as compared to the same from BMSCs. Th1/Th2/Th17 cytokine array revealed DPSC secretome had higher expression of the cytokines like GCSF, IFN?, and TGFß that promote neural differentiation. Thus, we concluded that DPSCs may be the preferred source of cells for obtaining neural lineage among the four sources of stem cells. Our results also indicate that the DPSC-secreted factors may be responsible for their propensity towards neural differentiation. This study suggests that DPSCs and their secretomes can be a potentially lucrative source for cell-based and "cell-free" (secretome) therapy for neural disorders and injury.


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06/20/2017 - Accelerated craniofacial bone regeneration through dense collagen gel scaffolds seeded with dental pulp stem cells.

Abstract


Therapies using mesenchymal stem cell (MSC) seeded scaffolds may be applicable to various fields of regenerative medicine, including craniomaxillofacial surgery. Plastic compression of collagen scaffolds seeded with MSC has been shown to enhance the osteogenic differentiation of MSC as it increases the collagen fibrillary density. The aim of the present study was to evaluate the osteogenic effects of dense collagen gel scaffolds seeded with mesenchymal dental pulp stem cells (DPSC) on bone regeneration in a rat critical-size calvarial defect model. Two symmetrical full-thickness defects were created (5mm diameter) and filled with either a rat DPSC-containing dense collagen gel scaffold (n=15), or an acellular scaffold (n=15). Animals were imaged in vivo by microcomputer tomography (Micro-CT) once a week during 5 weeks, whereas some animals were sacrificed each week for histology and histomorphometry analysis. Bone mineral density and bone micro-architectural parameters were significantly increased when DPSC-seeded scaffolds were used. Histological and histomorphometrical data also revealed significant increases in fibrous connective and mineralized tissue volume when DPSC-seeded scaffolds were used, associated with expression of type I collagen, osteoblast-associated alkaline phosphatase and osteoclastic-related tartrate-resistant acid phosphatase. Results demonstrate the potential of DPSC-loaded-dense collagen gel scaffolds to benefit of bone healing process.


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03/27/2017 - Osteoblastic differentiation of periodontal ligament stem cells on non-stoichiometric calcium phosphate and titanium surfaces.

Abstract


Bioactive materials offer particular clinical benefits in the field of dental implantology, where differentiation of stem cells towards an osteoblastic lineage is required for osseointegration and appropriate function of implants in vivo. The aim of this study was to evaluate the osteoblastic response of Stro-1 +ve periodontal ligament stem cells (PDLSCs) to three well-characterized biomaterial surfaces: an abraded titanium surface (cpTi) control; a polycrystalline titanium surface, with both micro and nanotopography produced by radio frequency magnetron sputtering (TiTi); and the same surface incorporating a sputter deposited calcium phosphate coating (CaP-TiTi). The CaP-TiTi surfaces were nonstoichiometric, carbonated, and calcium rich with a Ca/P ratio of 1.74. PDLSCs were grown on each surface in the absence of supplementary osteogneic-inducing agents. Osteoblastic responses were assessed for up to 21 days in culture by measuring gene expression using real time q-PCR and via assessment of intracellular alkaline phosphatase (ALP) activity. Gene expression analysis for the CaP-TiTi surfaces showed a significant late stage up-regulation of Secreted Phosphoprotein 1. Additionally, there was a significant up-regulation of the Wnt signaling genes ß-catenin and Wnt Family Member 5 A on days 14 and 21, respectively for the CaP-TiTi surface. A significant increase in intracellular ALP at day 21 for the CaP-TiTi surface was also observed. These data suggest that the CaP-TiTi surfaces provide the bioactive conditions required for direct osteoblastic differentiation of PDLSCs. 


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03/17/2017 - Novel Cryopreservation Method for the Effective Collection of Dental Pulp Stem Cells.

Abstract

Dental pulp stem cells (DPSCs) are an attractive cell source for use in cell-based therapy, regenerative medicine, and tissue engineering because DPSCs have high cell proliferation ability and multi-differentiation capacity. However, several problems are associated with the collection and preservation of DPSCs for future cell-based therapy. In addition, the isolation of DPSCs for cryopreservation is time-consuming and expensive. In this study, we developed a novel cryopreservation method for dental pulp tissues that can isolate suitable DPSCs after thawing cryopreserved tissue. Using the novel cryopreservation method, dental pulp tissues were cultured on adhesion culture dishes for 5 days and then cryopreserved. After thawing, the cryopreserved dental pulp tissue fragments exhibited cell migration. We evaluated each property of DPSCs isolated using the novel cryopreservation method (DPSCs-NCM) and the explant method alone without cryopreservation (DPSCs-C). DPSCs-NCM had the same proliferation capacity as DPSCs-C. FACS analysis indicated that both DPSCs-NCM and DPSCs-C were positive for mesenchymal stem cell markers at the same level but negative for hematopoietic cell markers. Moreover, both DPSCs-NCM and DPSCs-C could differentiate into osteogenic, chondrogenic, and adipogenic cells during culture in each induction medium. These results suggest that DPSCs-NCM may be mesenchymal stem cells. Therefore, our novel method might allow for easy and less expensive cryopreservation of DPSCs, thereby providing suitable DPSCs for use in patients in future cell-based therapies.


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10/14/2016 - Effects of nanoporous anodic titanium oxide on human adipose derived stem cells

Abstract


The aim of current bone biomaterials research is to design implants that induce controlled, guided, successful, and rapid healing. Titanium implants are widely used in dental, orthopedic, and reconstructive surgery. A series of studies has indicated that cells can respond not only to the chemical properties of the biomaterial, but also, in particular, to the changes in surface topography. Nanoporous materials remain in focus of scientific queries due to their exclusive properties and broad applications. One such material is nanostructured titanium oxide with highly ordered, mutually perpendicular nanopores. Nanoporous anodic titanium dioxide (TiO2) films were fabricated by a three-step anodization process in propan-1,2,3-triol-based electrolyte containing fluoride ions. Adipose-derived stem cells offer many interesting opportunities for regenerative medicine. The important goal of tissue engineering is to direct stem cell differentiation into a desired cell lineage. The influence of nanoporous TiO2 with pore diameters of 80 and 108 nm on cell response, growth, viability, and ability to differentiate into osteoblastic lineage of human adipose-derived progenitors was explored. Cells were harvested from the subcutaneous abdominal fat tissue by a simple, minimally invasive, and inexpensive method. Our results indicate that anodic nanostructured TiO2 is a safe and nontoxic biomaterial. In vitro studies demonstrated that the nanotopography induced and enhanced osteodifferentiation of human adipose-derived stem cells from the abdominal subcutaneous fat tissue.


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10/01/2016 - Does Cryopreservation Affect the Biological Properties of Stem Cells from Dental Tissues? A Systematic Review

Abstract

This systematic review evaluated if different cryopreservation protocols could affect biological properties (Cell survival rate (CSR), proliferation, differentiation, maintenance of stem cell markers) of stem cells obtained from dental tissues (DSC) post-thaw. An electronic search was carried out within PubMed and ISI Web Science by using specific keyword. Two independent reviewers read the titles and abstracts of all reports respecting predetermined inclusion/exclusion criteria. Data were extracted considering the biological properties of previously cryopreserved DSCs and previously cryopreserved dental tissues. DSCs cryopreserved as soon as possible after their isolation presents a CSR quite similar to the non-cryopreserved DSC. Dimethyl sulfoxide (DMSO) [10%] showed good results related to cell recovery post-thaw to cryopreserve cells and tissues for periods of up to 2 years. The cryopreservation of DSC in a mechanical freezer (-80°C) allows the recovery of stem cells post-thaw. The facilities producing magnetic field (MF), demand a lower concentration of cryoprotectant, but their use is not dispensable. It is possible to isolate and cryopreserve dental pulp stem cell (DPSC) from healthy and diseased vital teeth. Cryopreservation of dental tissues for late DSC isolation, combined with MF dispensability, could be valuable to reduce costs and improve the logistics to develop teeth banks.


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05/03/2016 - Isolation of dental pulp stem cells from a single donor and characterization of their ability to differentiate after 2 years of cryopreservation

Abstract

OBJECTIVES:

To investigate the viability and differentiation capacity of dental pulp stem cells (DPSCs) isolated from single donors after 2 years of cryopreservation.  

METHODS:

This prospective study was conducted between October 2010 and February 2014 in the Stem Unit, College of Medicine, King Saud University, Riyadh, Saudi Arabia. Seventeen teeth extracted from 11 participants were processed separately to assess the minimum tissue weight needed to yield cells for culturing in vitro. Cell stemness was evaluated before passage 4 using the colony forming unit assay, immunofluorescence staining, and bi-lineage differentiation. Dental pulp stem cells  were cryopreserved for 2 years. Post-thaw DPSCs were cultured until senescence and differentiated toward osteogenic, odontogenic, adipogenic, and chondrogenic lineages.  

RESULTS:

Viable cells were isolated successfully from 6 of the 11 participants. Three of these 6 cultured cell lines were identified as DPSCs. A minimum of 0.2 g of dental pulp tissue was required for successful isolation of viable cells from a single donor. Post-thaw  DPSCs successfully differentiated towards osteogenic, odontogenic, chondrogenic, and adipogenic lineages. The post-thaw DPSCs were viable in vitro up to 70 days before senescence. There was no significant difference between the cells.  

CONCLUSION:

Within the limitations of this investigation, viable cells from dental pulp tissue were isolated successfully from the same donor using a minimum of 2 extracted teeth. Not all isolated cells from harvested dental pulp tissue had the characteristics of DPSCs. Post-thaw DPSCs maintained their multi-lineage differentiation capacity.


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01/01/2016 - Cryopreservation and Banking of Dental Stem Cells

Abstract

Over the past decade, dental tissues have become an attractive source of mesenchymal stem cells (MSCs). Dental stem cells (DSCs) are not only able to differentiate into adipogenic, chondrogenic and osteogenic lineanges, but an increasing amount of research also pointed out their potential applicability in numerous clinical disorders, such as myocardial infarction, neurodegenerative diseases and diabetes. Together with their multilineage differentiation capacity, their easy availability from extracted third molars makes these stem cells a suitable alternative for bone marrow-derived MSCs. More importantly, DSCs appear to retain their stem cell properties following cryopreservation, a key aspect in their long-term preservation and upscale production. However, the vast number of different cryopreservation protocols makes it difficult to draw definite conclusions regarding the behavior of these stem cells. The routine application and banking of DSCs is also associated with some other pitfalls, such as interdonor variability, cell culture-induced changes and the use of animal-derived culture medium additives. Only thorough assessment of these challenges and the implementation of standardized, GMP procedures will successfully lead to better treatment options for patients who no longer benefit from current stem cell therapies.


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09/04/2015 - Dental Pulp Stem Cells: A New Cellular Resource for Corneal Stromal Regeneration
Abstract

Corneal blindness afflicts millions of individuals worldwide and is currently treated by grafting with cadaveric tissues; however, there are worldwide donor tissue shortages, and many allogeneic grafts are eventually rejected. Autologous stem cells present a prospect for personalized regenerative medicine and an alternative to cadaveric tissue grafts. Dental pulp contains a population of adult stem cells and, similar to corneal stroma, develops embryonically from the cranial neural crest. We report that adult dental pulp cells (DPCs) isolated from third molars have the capability to differentiate into keratocytes, cells of the corneal stoma. After inducing differentiation in vitro, DPCs expressed molecules characteristic of keratocytes, keratocan, and keratan sulfate proteoglycans at both the gene and the protein levels. DPCs cultured on aligned nanofiber substrates generated tissue-engineered, corneal stromal-like constructs, recapitulating the tightly packed, aligned, parallel fibrillar collagen of native stromal tissue. After injection in vivo into mouse corneal stroma, human DPCs produced corneal stromal extracellular matrix containing human type I collagen and keratocan and did not affect corneal transparency or induce immunological rejection. These findings demonstrate a potential for the clinical application of DPCs in cellular or tissue engineering therapies for corneal stromal blindness.

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09/04/2015 - Adhesion and Proliferation of Human Dental Pulp Stem Cells on Porous Silicon Scaffolds
Abstract

In regenerative medicine, stem-cell-based therapy often requires a scaffold to deliver cells and/or growth factors to the injured site. Porous silicon (pSi) is a promising biomaterial for tissue engineering as it is both nontoxic and bioresorbable. Moreover, surface modification can offer control over the degradation rate of pSi and can also promote cell adhesion. Dental pulp stem cells (DPSC) are pluripotent mesenchymal stem cells found within the teeth and constitute a readily source of stem cells. Thus, coupling the good proliferation and differentiation capacities of DPSC with the textural and chemical properties of the pSi substrates provides an interesting approach for therapeutic use. In this study, the behavior of human DPSC is analyzed on pSi substrates presenting pores of various sizes, 10 ± 2 nm, 36 ± 4 nm, and 1.0 ± 0.1 µm, and undergoing different chemical treatments, thermal oxidation, silanization with aminopropyltriethoxysilane (APTES), and hydrosilylation with undecenoic acid or semicarbazide. DPSC adhesion and proliferation were followed for up to 72 h by fluorescence microscopy, scanning electron microscopy (SEM), enzymatic activity assay, and BrdU assay for mitotic activity. Porous silicon with 36 nm pore size was found to offer the best adhesion and the fastest growth rate for DPSC compared to pSi comporting smaller pore size (10 nm) or larger pore size (1 µm), especially after silanization with APTES. Hydrosilylation with semicarbazide favored cell adhesion and proliferation, especially mitosis after cell adhesion, but such chemical modification has been found to led to a scaffold that is stable for only 24–48 h in culture medium. Thus, semicarbazide-treated pSi appeared to be an appropriate scaffold for stem cell adhesion and immediate in vivo transplantation, whereas APTES-treated pSi was found to be more suitable for long-term in vitro culture, for stem cell proliferation and differentiation.

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09/04/2015 - Postnatal epithelium and mesenchyme stem/progenitor cells in bioengineered amelogenesis and dentinogenesis

Abstract

Rodent incisors provide a classic model for studying epithelial–mesenchymal interactions in development. However, postnatal stem/progenitor cells in rodent incisors have not been exploited for tooth regeneration. Here, we characterized postnatal rat incisor epithelium and mesenchyme stem/progenitor cells and found that they formed enamel- and dentin-like tissues in vivo. Epithelium and mesenchyme cells were harvested separately from the apical region of postnatal 4–5 day rat incisors. Epithelial and mesenchymal phenotypes were confirmed by immunocytochemistry, CFU assay and/or multi-lineage differentiation. CK14+, Sox2+ and Lgr5+ epithelium stem cells from the cervical loop enhanced amelogenin and ameloblastin expression upon BMP4 or FGF3 stimulation, signifying their differentiation towards ameloblast-like cells, whereas mesenchyme stem/progenitor cells upon BMP4, BMP7 and Wnt3a treatment robustly expressed Dspp, a hallmark of odontoblastic differentiation. We then control-released microencapsulated BMP4, BMP7 and Wnt3a in transplants of epithelium and mesenchyme stem/progenitor cells in the renal capsule of athymic mice in vivo. Enamel and dentin-like tissues were generated in two integrated layers with specific expression of amelogenin and ameloblastin in the newly formed, de novo enamel-like tissue, and DSP in dentin-like tissue. These findings suggest that postnatal epithelium and mesenchyme stem/progenitor cells can be primed towards bioengineered tooth regeneration.



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09/04/2015 - Isolation and characterization of human dental pulp derived stem cells
Background: Dental caries remains a major public health concern. Dental endodontics (root canal) therapy involves extirpating the dental pulp and replacing with inert materials. For severe tooth decay, it is the only available treatment; however, it fails to restore the biological functions and vitality of the dental tissues and may ultimately leads to tooth loss. To overcome these shortcomings, dental pulp stem cells (DPSCs) are being investigated as a novel prospective approach to regenerate the dental tissue. In this study, we isolated and purified DPSCs and characterized the purified cells.

Objectives: The aims of this study were as follows: (i) to rapidly extirpate dental pulp tissues from human third molar teeth under sterile conditions; (ii) to isolate, characterize, and purify a heterogeneous population of DPSCs using mesenchymal stem cell markers; (iii) to determine the ability of DPSCs to differentiate down an odontoblastic lineage.

Design: DPSCs were mechanically and chemically isolated from human impacted third molar teeth. Cells were expanded, passaged, and a heterogeneous population of DPSCs isolated using a cloning cylinder. DPSCs were characterized and purified by flow cytometry using the mesenchymal stem cell markers, STRO-1, CD44, and CD146. DPSCs were induced under two different odontogenic conditions comprising different concentrations of beta-glycerophosphate, and dexamethasone. DPSCs were analysed for morphology, proliferation potential, collagen formation, mineralization characteristics, and expression of the dentin-specific markers dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP-1), using immunohistochemistry.

Results: DPSCs were positive for the mesenchymal stem cell markers STRO-1, CD44, and CD146, although two populations of cells showed different levels of STRO-1 expression. Differentiated DPSCs (dDPSCs) demonstrated a significant increase in alkaline phosphatase concentration between days 14 and 21, while a similar increase in collagen deposition, mineralization, and calcification was also observed on day 28. The proliferation rate of dDPSCs decreased with time. Odontoblast characteristics of dDPSCs were observed, with increased expression of the dentin-specific markers DSPP and DMP-1.

Conclusions: This investigation demonstrated successful isolation of DPSCs and differentiation of DPSCs down an odontoblastic lineage, indicating that DPSCs represent a promising approval for the regeneration of lost dental tissues.

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09/04/2015 - Human Dental Pulp Stem Cells Improve Hypoxic-Ischemic Brain Damage
Abstract

Objective To investigate the effect of intraventricular injection of human dental pulp stem cells (DPSCs) on hypoxic-ischemic brain damage (HIBD).

Methods Thirty-six neonatal animal models (postnatal day 7) were assigned to control, HIBD, or HIBD+DPSC groups (n = 12 each group). For induction of HIBD, models underwent left carotid artery ligation and were exposed to 8% to 10% oxygen for 2 h. Hoechst 33324-labeled human DPSCs were injected into the left lateral ventricle 3 days after HIBD. Behavioral assays were performed to assess hypoxic-ischemic encephalopathy (HIE), and on postnatal day 45, DPSC survival was assessed and expression of neural and glial markers was evaluated by immunohistochemistry and Western blot.

Results The HIBD group showed significant deficiencies compared to control on T-maze, radial water maze, and postural reflex tests, and the HIBD+DPSC group showed significant improvement on all behavioral tests. On postnatal day 45, Hoechst 33324-labeled DPSC nuclei were visible in the injected region and left cortex. Subsets of DPSCs showed immunostaining for neuronal (neuron-specific enolase [NSE], Nestin) and glial markers (glial fibrillary acidic protein [GFAP], O4). Significantly decreased staining/expression for NSE, GFAP, and O4 was found in the HBID group compared to control, and this was significantly increased in the HBID+DPSC group.

Conclusion Intraventricular injection of human DPSCs improves HIBD in neonatal rats.

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01/01/2015 - Evaluation of two human dental pulp stem cell cryopreservation methods

Abstract

Dental pulp is a promising source of mesenchymal stem cells for use in cell therapy and regenerative medicine. Methods for storing stem cells with minimum compromise of cell viability, differentiation capacity and function should be developed for clinical and research applications. The aim of this study was to evaluate whether human dental pulp stem cells (hDPSCs) isolated and cryopreserved for 1, 7 and 30 days maintain viability and expression of specific stem cell markers. Human dental pulp stem cells were isolated from 23 healthy patients aged 18 to 31 years. Dental pulp was enzymatically dissociated, and CD105+ cells were separated using the Miltenyi™ system. The hDPSCs were cryopreserved using the Kamath and Papaccio methods. Post-cryopreservation viability was measured by flow cytometry (7AAD) and by the expression of the phenotype markers CD105+/ CD73+, CD34-/CD45-. The Papaccio method showed greater cell viability for cells that had been frozen for 30 days (59.5%) than the Kamath method (56.2%), while the Kamath method provided better results for 1 day (65.5%) and 7 days (56%). Post-cryopreservation expression of the markers CD105+/CD34- was greater after 1 and 7 days with the Kamath method and CD105+/CD45- were expressed after all 3 cryopreservation times. There was greater expression of CD73+ in the hDPSCs after 1 and 7 days with the Kamath method, and after 30 days with the Papaccio method. These results suggest that hDPSCs express mesenchymal stem cell markers after cryopreservation. However, cryopreservation time may affect marker expression, probably by altering the spatialconfiguration of cell membrane proteins or by compromising cells at a certain level of differentiation.

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02/11/2014 - Adult Human Stem Cells as a Source for Whole-tooth Bioengineering
Abstract

Teeth develop from interactions between embryonic oral epithelium and neural-crest-derived mesenchyme. These cells can be separated into single-cell populations and recombined to form normal teeth, providing a basis for bioengineering new teeth if suitable, non-embryonic cell sources can be identified. We show here that cells can be isolated from adult human gingival tissue that can be expanded in vitro and, when combined with mouse embryonic tooth mesenchyme cells, form teeth. Teeth with developing roots can be produced from this cell combination following transplantation into renal capsules. These bioengineered teeth contain dentin and enamel with ameloblast-like cells and rests of Malassez of human origin.

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11/18/2013 - Multilineage potential and proteomic profiling of human dental stem cells derived from a single donor.
Source

Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea.

Abstract

Dental tissues provide an alternative autologous source of mesenchymal stem cells (MSCs) for regenerative medicine. In this study, we isolated human dental MSCs of follicle, pulp and papilla tissue from a single donor tooth after impacted third molar extraction by excluding the individual differences. We then compared the morphology, proliferation rate, expression of MSC-specific and pluripotency markers, and in vitro differentiation ability into osteoblasts, adipocytes, chondrocytes and functional hepatocyte-like cells (HLCs). Finally, we analyzed the protein expression profiles of undifferentiated dental MSCs using 2DE coupled with MALDI-TOF-MS. Three types of dental MSCs largely shared similar morphology, proliferation potential, expression of surface markers and pluripotent transcription factors, and differentiation ability into osteoblasts, adipocytes, and chondrocytes. Upon hepatogenic induction, all MSCs were transdifferentiated into functional HLCs, and acquired hepatocyte functions by showing their ability for glycogen storage and urea production. Based on the proteome profiling results, we identified nineteen proteins either found commonly or differentially expressed among the three types of dentalMSCs. In conclusion, three kinds of dental MSCs from a single donor tooth possessed largely similar cellular properties and multilineage potential. Further, these dental MSCs had similar proteomic profiles, suggesting their interchangeable applications for basic research and cell therapy.

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08/27/2013 - Use of Mesenchymal Stem Cells for Alveolar Bone Tissue Engineering for Cleft Lip and Palate Patients

The reconstruction of the craniofacial skeleton in development between 2 and 10 years old, remains a major challenge for reconstructive plastic surgery. Local autogenous bone is practically unavailable, the distant bone graft has significant morbidity and use of alloplastic materials is incompatible with the growing facial skeleton. With the advent of bioengineered tissue, however, osteogenesis induced by the use of mesenchymal stem cells associated with biomaterials has become a potential solution to the shortage bone-related morbidity and donor bone in the region in pediatric patients.

The association of mesenchymal stem cells to biomaterials has provided new bone formation and a significant reduction of morbidity, for rehabilitation of the alveolar bone in patients with cleft lip palate.

To perform the rehabilitation of alveolar bone cleft, other donor regions of bone (iliac crest, ribs, skull) suffer morbidity for obtaining bone to be used in alveolar bone grafting. In order to eliminate the morbidity at the bone donor region for these patients and reduce costs of patient permanence in the operating room the aim of this study is to perform the bone tissue engineering to reconstruct the alveolar bone defect in cleft lip and palate patients using mesenchymal stem cells from deciduous dental pulp associated with a collagen and hydroxyapatite biomaterial (Geistlich Bio-Oss®) through prospective qualitative and quantitative analysis of bone neoformation.


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04/22/2013 - Regeneration of dental pulp tissue in immature teeth with apical periodontitis using platelet-rich plasma and dental stem cells
Abstract: Aim To investigate the new tissues growing into the pulp space of immature dog teeth that were infected, disinfected and filled with blood clot (BC), dental pulp cells (DPCs), platelet-rich plasma (PRP) or a combination of DPCs and PRP in immature dog teeth with apical periodontitis.

Methodology: Fifty-six immature roots from mandibular premolars of four beagles were divided into four experimental groups (n = 40) and two control groups. After the induction of apical periodontitis, the root canals of experimental groups were disinfected with NaOCl irrigation and a tri-antibiotic paste medication. The canals were then filled with different materials according to the experimental group: BC group, DPCs group, PRP group or DPCs + PRP group. Access cavities were sealed with MTA and composite. Radiographs were taken after 90 days, and the jaws including the teeth were processed for histologic analysis. The data were statistically analysed using chi-square evaluation and Student's t-test.

Results: Radiographic analyses demonstrated no significant difference between experimental groups in periradicular bone healing (P > 0.05), whilst those groups that used DPCs produced a significantly greater root thickening (P < 0.01). The histologic evaluation showed that the groups with PRP formed more tissues in the canals (P = 0.01). The groups with DPCs had substantially more mineralized tissue formation in the canal than those without DPCs, especially in the apical third. In DPCs + PRP group, bone-like tissue grew into the canal space from the periapical tissue.

Conclusions: A combination of DPCs + PRP increased vital tissue regeneration within the root canals of immature teeth associated with apical periodontitis. Regeneration of Dental Pulp Tissue Full Text
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01/27/2013 - Stem cells in the face: tooth regeneration and beyond.
The face distinguishes one person from another. Postnatal orofacial tissues harbor rare cells that exhibit stem cell properties. Despite unmet clinical needs for reconstruction of tissues lost in congenital anomalies, infections, trauma, or tumor resection, how orofacial stem/progenitor cells contribute to tissue development, pathogenesis, and regeneration is largely obscure. This perspective article critically analyzes the current status of our understanding of orofacial stem/progenitor cells, identifies gaps in our knowledge, and highlights pathways for the development of regenerative therapies. Stem Cells in Face: Tooth Regeneration Full Text
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07/24/2012 - In vitro analysis of mesenchymal stem cells derived from human teeth and bone marrow
Mesenchymal stem cells derived from human teeth and bone marrow have been characterized by many research groups, but demonstrate inconsistent cellular phenotypes or functions, partly because of differences in culture methodology. Therefore, our aims were to resolve these inconsistencies and discuss the potential uses of these cells in research/clinical applications. We isolated and characterized dental stem cells (DSCs) from the dental pulp, periodontal ligament, apical papilla (APSCs) and dental follicle (DFSCs) of mature and immature teeth, along with bone marrow-derived stem cells (BMSCs) from the iliac crest. We compared the clonogenic and proliferative potentials of these cells in terms of colony-forming efficiency, proliferation potential, population doubling time and cell cycle. All DSCs, particularly APSCs and DFSCs, possessed greater proliferative potential than BMSCs. All stem cells expressed typical mesenchymal and embryonic markers, and developed alizarin red-positive mineralization nodules and Oil red O-positive lipid droplets when cultured in osteogenic and adipogenic media, respectively. Immunocytochemistry revealed that all stem cells developed neuronal markers when cultured in a control medium without neural inductive supplements. After 7 days of neurogenic culture, the differentiated cells showed a transition from fibroblast-like to neuron-like cell bodies with long processes, suggesting that the stem cells differentiated into mature neurons. Karyotyping confirmed that the stem cells maintained a normal karyotype and were chromosomally stable. Our results provide new insights into the physiological properties of stem cells with a normal karyotype and indicate that DSCs are appropriate for basic research and clinical applications.

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07/11/2012 - Scaling-Up of Dental Pulp Stem Cells Isolated from Multiple Niches
Dental pulp (DP) can be extracted from child’s primary teeth (deciduous), whose loss occurs spontaneously by about 5 to 12 years. Thus, DP presents an easy accessible source of stem cells without ethical concerns. Substantial quantities of stem cells of an excellent quality and at early (2–5) passages are necessary for clinical use, which currently is a problem for use of adult stem cells. Herein, DPs were cultured generating stem cells at least during six months through multiple mechanical transfers into a new culture dish every 3–4 days. We compared stem cells isolated from the same DP before (early population, EP) and six months after several mechanical transfers (late population, LP). No changes, in both EP and LP, were observed in morphology, expression of stem cells markers (nestin, vimentin, fibronectin, SH2, SH3 and Oct3/4), chondrogenic and myogenic differentiation potential, even after cryopreservation. Six hours after DP extraction and in vitro plating, rare 5-bromo-2'-deoxyuridine (BrdU) positive cells were observed in pulp central part. After 72 hours, BrdU positive cells increased in number and were found in DP periphery, thus originating a multicellular population of stem cells of high purity. Multiple stem cell niches were identified in different zones of DP, because abundant expression of nestin, vimentin and Oct3/4 proteins was observed, while STRO-1 protein localization was restricted to perivascular niche. Our finding is of importance for the future of stem cell therapies, providing scaling-up of stem cells at early passages with minimum risk of losing their “stemness”.

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03/09/2012 - Researchers Differentiate Dental Pulp Stem Cells into Liver Cells
Researchers from Nippon Dental University, Japan, have developed a method to boost the ability of dental stem cells to differentiate into hepatic (liver) cells.  The protocols developed by the researchers produced hepatic cells [from dental stem cells] in significantly high numbers and purity. The research demonstrates that stem cells from teeth are a reliable source of adult stem cell for future liver-cell therapies.

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02/29/2012 - Dental Pulp Stem Cells Restore Movement in Spinal Cord Injuries

Researchers at the Nagoya University Graduate School of Medicine in Japan are exploiting the neural capabilities of dental pulp stem cells obtained from human wisdom teeth. In the study, researchers used stem cells recovered from wisdom teeth to treat a rat population with transected spinal cords. The rats were found to have recovered locomotive function in their hind legs and regenerated damaged nerve cells and oligodendrocytes. In a parallel study, stem cells from bone marrow and skin fibroblasts were utilized with statistically significantly lesser effect.

As the study demonstrates, teeth are a valuable source of powerful stem cells. Banking your own adult stem cells today will insure your future health as regenerative therapies, such as these, are developed to treat a wide array of disease, trauma and injury.

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01/04/2012 - Differentiation of dental pulp stem cells into islet-like aggregates.
The post-natal dental pulp tissue contains a population of multipotent mesenchymal progenitor cells known as dental pulp stromal/stem cells (DPSCs), with high proliferative potential for self-renewal. In this investigation, we explored the potential of DPSCs to differentiate into pancreatic cell lineage resembling islet-like cell aggregates (ICAs). We isolated, propagated, and characterized DPSCs and demonstrated that these could be differentiated into adipogenic, chondrogenic, and osteogenic lineage upon exposure to an appropriate cocktail of differentiating agents. Using a three-step protocol reported previously by our group, we succeeded in obtaining ICAs from DPSCs. The identity of ICAs was confirmed as islets by dithiozone-positive staining, as well as by expression of C-peptide, Pdx-1, Pax4, Pax6, Ngn3, and Isl-1. There were several-fold up-regulations of these transcription factors proportional to days of differentiation as compared with undifferentiated DPSCs. Day 10 ICAs released insulin and C-peptide in a glucose-dependent manner, exhibiting in vitro functionality. Our results demonstrated for the first time that DPSCs could be differentiated into pancreatic cell lineage and offer an unconventional and non-controversial source of human tissue that could be used for autologous stem cell therapy in diabetes.

Source - Stempeutics Research Malaysia Sdn Bhd, (773817-K), Lot G-E-2A, Enterprise 4, Technology Park Malaysia, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
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12/06/2011 - Dental Stem Cells Promote Spinal Cord Regeneration After Injury
Recently, a team of researchers at the Nagoya University Graduate School of Medicine, motivated by the knowledge that stem cells taken from tooth pulp are capable of stimulating long-term regeneration of nerves in damaged spinal cords, tested the ability of dental stem cells to treat said injuries. The results have positively demonstrated that dental stem cells not only “promoted the   regeneration of transected axons by directly inhibiting multiple axon growth inhibitors,” but also, “prevented a damage-induced apoptosis,” and were able to replaced the original cells that were lost due to injury.

“To our knowledge, the latter two neuroregenerative activities are unique to tooth-derived stem cells and are not exhibited by any other previously described stem cells,” the researchers stated. “We propose that tooth-derived stem cells may be an excellent and practical cellular resource for the treatment of SCI [spinal cord injury].”

The era of regenerative medicine is now.

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11/13/2011 - Stem cells in dental pulp of deciduous teeth
Dental pulp from deciduous (baby) teeth, which are discarded after exfoliation, represents an advantageous source of young stem cells. Herein, we discuss the methods of Deciduous Teeth Stem Cells (DTSCs) isolation and cultivation. We show that based on these methods, at least three different stem cells populations can be identified: a population similar to bone marrow derived mesenchymal stem cells (BM-MSCs), an epithelial stem-like cells (ESCs) and/or a mixed population composed of both cell types. We analyzed the embryonic origin and stem cell niche of DTSCs with respect to the advantages they can provide for their future use in cell therapies and regenerative medicine. In vitro and in vivo differentiation of the DTSCs populations, their developmental potential, immunological compatibility, tissues engineering, transplantation use in studies in animal models are also the focus of the present report. We briefly describe the derivation of induced pluripotent stem (iPS) cells from DTSCs, which can be obtained more easily and efficiently in comparison with human fibroblasts. These iPS cells represent an interesting model for the investigation of pediatric diseases and disorders. The importance of DTSCs banking is also discussed.

Butantan, Genetics, av. Vital Brasil, 1500, São Paulo, Brazil, 05503-900, 55 11 3726 7222; ikerkis@butantan.gov.br.

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10/28/2011 - Human dental pulp cells: a new source of cell therapy in a mouse model of compressive spinal cord injury.
J Neurotrauma. 2011 Sep;28(9):1939-49. Epub 2011 Aug 8.

Programa de Pesquisa em Neurociência Básica e Clínica, Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Brazil.

Strategies aimed at improving spinal cord regeneration after trauma are still challenging neurologists and neuroscientists throughout the world. Many cell-based therapies have been tested, with limited success in terms of functional outcome. In this study, we investigated the effects of human dental pulp cells (HDPCs) in a mouse model of compressive spinal cord injury (SCI). These cells present some advantages, such as the ease of the extraction process, and expression of trophic factors and embryonic markers from both ecto-mesenchymal and mesenchymal components. Young adult female C57/BL6 mice were subjected to laminectomy at T9 and compression of the spinal cord with a vascular clip for 1?min. The cells were transplanted 7 days or 28 days after the lesion, in order to compare the recovery when treatment is applied in a subacute or chronic phase. We performed quantitative analyses of white-matter preservation, trophic-factor expression and quantification, and ultrastructural and functional analysis. Our results for the HDPC-transplanted animals showed better white-matter preservation than the DMEM groups, higher levels of trophic-factor expression in the tissue, better tissue organization, and the presence of many axons being myelinated by either Schwann cells or oligodendrocytes, in addition to the presence of some healthy-appearing intact neurons with synapse contacts on their cell bodies. We also demonstrated that HDPCs were able to express some glial markers such as GFAP and S-100. The functional analysis also showed locomotor improvement in these animals. Based on these findings, we propose that HDPCs may be feasible candidates for therapeutic intervention after SCI and central nervous system disorders in humans.

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10/28/2011 - Feeder-free derivation of induced pluripotent stem cells from human immature dental pulp stem cells.
Cell Transplant. 2011 Apr 1.


Induced pluripotent stem cells (iPSC) can be created by forcing expression of certain genes in fibroblasts or other somatic cell types, reversing them to a pluripotent state similar to that of embryonic stem cells (ESC). Here, we used human immature dental pulp stem cells (hIDPSC) as an alternative source for creating iPSC. HIDPSC can be easily isolated from accessible tissue of young and adult patients. HIDPSC possess a fibroblast-like morphology, retaining characteristics of adult multipotent stem cells. Reprogramming of hIDPSC was fast, producing primary hIDPSC-iPSC colonies even under feeder-free conditions. hIDPSC acquired ESC-like morphology, expressed pluripotent markers, possessed stable, normal karyotypes and demonstrate the ability to differentiated in vitro and in vivo. Our data demonstrate that hIDPSC-iPSC offer an advantageous cell system for future cell therapy and basic studies, particularly as a model for pediatric developmental disorders.

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09/03/2011 - Human dental pulp stem cells demonstrate better neural and epithelial stem cell properties than bone marrow-derived mesenchymal stem cells.

Department of Stem Cell, Center for Stem Cell and Gene Therapies Research and Practice, Institute of Health Sciences, Kocaeli University, 41380, Kocaeli, Turkey, ekaraoz@hotmail.com.

Dental pulp stem cells (hDP-SCs) were primarily derived from pulp tissues of primary incisors, exfoliated deciduous and permanent third molar teeth. To understand the characteristics of hDP-SCs from impacted third molar, proliferation capacities, gene expression profiles, phenotypic, ultrastructural, and differentiation characteristics were analyzed in comparison with human bone marrow-derived mesenchymal stem cells (hBM-MSCs), extensively. hDP-SCs showed more developed and metabolically active cells. Contrary to hBM-MSCs, hDP-SCs strongly expressed both cytokeratin (CK)-18 and -19, which could involve in odontoblast differentiation and dentine repair. The intrinsic neuro-glia characteristics of hDP-MSCs were demonstrated by the expression of several specific transcripts and proteins of neural stem cell and neurons. These cells not only differentiate into adipogenic, osteogenic, and chondrogenic lineage, but also share some special characteristics of expressing some neural stem cell and epithelial markers. Under defined conditions, hDP-SCs are able to differentiate into both neural and vascular endothelial cells in vitro. Dental pulp might provide an alternative source for human MSCs. hDP-SCs with a promising differentiation capacity could be easily isolated, and possible clinical use could be developed for neurodegenerative and oral diseases in the future.

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07/30/2011 - Differentiation and Neuro-Protective Properties of Immortalized Human Tooth Germ Stem Cells.
Neurochem Res. 2011 Jul 22.

Department of Genetics and BioEngineering, College of Engineering and Architecture, Yeditepe University, 26 Agustos Campus, Kayisdagi cad, Kayisdagi, 34755, Istanbul, Turkey.

Stem cells are considered to be promising therapeutic options in many neuro-degenerative diseases and injuries to the central nervous system, including brain ischemia and spinal cord trauma. Apart from the gold standard embryonic and mesenchymal origin, human tooth germ stem cells (hTGSCs) have also been shown to enjoy the characteristics of mesenchymal stem cells (MSCs) and the ability to differentiate into adipo-, chondro-, osteo- and neuro-genic cells, suggesting that they might serve as potential alternatives in the cellular therapy of various maladies. Immortalization of stem cells may be useful to avoid senescence of stem cells and to increase their proliferation potential without altering their natural characteristics. This study evaluated the expression of stem cell markers, surface antigens, differentiation capacity, and karyotype of hTGSCs that have been immortalized by human telomerase reverse transcriptase (hTERT) or simian vacuolating virus 40 (SV40) large T antigen. These undying cells were also evaluated for their neuro-protective potential using an in vitro SH-SY5Y neuro-blastoma model treated with hydrogen-peroxide or doxo-rubicin. Although hTGSC-SV40 showed abnormal karyotypes, our results suggest that hTGSC-hTERT preserve their MSC characteristics, differentiation capacity and normal karyotype, and they also possess high proliferation rate and neuro-protective effects even at great passage numbers. These peculiars indicate that hTGSC-hTERT could be used as a viable model for studying adipo-, osteo-, odonto- and neuro-genesis, as well as neuro-protection of MSCs, which may serve as a springboard for potentially utilizing dental waste material in cellular therapy.

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07/30/2011 - Isolation of pluripotent stem cells from human third molar dental pulp.
Histol Histopathol. 2011 Aug;26(8):1057-70.

Regenerative Medicine Laboratory, Universitat Internacional de Catalunya, Barcelona, Spain.

Potent stem/progenitor cells have been isolated from normal human dental pulps, termed dental pulp stem cells (DPSCs). However, no study has described the presence of stem cell populations in human dental pulp from the third molar with embryonic phenotypes. The dental pulp tissue was cultured in media with the presence of LIF, EGF, and PDGF. In the present study, we describe a new population of pluripotent stem cells that were isolated from dental pulp (DPPSC). These cells are SSEA-4+, Oct4+, Nanog+, FLK-1+, HNF3beta+, Nestin+, Sox2+, Lin28+, c-Myc+, CD13+, CD105+, CD34-, CD45-, CD90low, CD29+, CD73low, STRO-1low and CD146-. We have investigated by SEM analysis and q-RT-PCR the capacity of DPPSCs to 3D differentiate in vitro using the Cell Carrier 3D glass scaffold into tissues that have similar characteristics to embryonic mesoderm and endoderm layers. These data would support the use of these cells, which are derived from an easily accessible source and can be used in future regeneration protocols for many tissue types that differentiate from the three embryonic layers.

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07/30/2011 - Soft matrix supports osteogenic differentiation of human dental follicle cells.
Biochem Biophys Res Commun. 2011 Jul 8;410(3):587-92. Epub 2011 Jun 12.

Source

Department of Operative Dentistry and Periodontology, University Hospital Regensburg, Regensburg, Germany.

Abstract

The differentiation of stem cells can be directed by the grade of stiffness of the developed tissue cells. For example a rigid extracellular matrix supports the osteogenic differentiation in bone marrow derived mesenchymal stem cells (MSCs). However, less is known about the relation of extracellular matrix stiffness and cell differentiation of ectomesenchymal dental precursor cells. Our study examined for the first time the influence of the surface stiffness on the proliferation and osteogenic differentiation of human dental follicle cells (DFCs). Cell proliferation of DFCs was only slightly decreased on cell culture surfaces with a bone-like stiffness. The osteogenic differentiation in DFCs could only be initiated with a dexamethasone based differentiation medium after using varying stiffness. Here, the softest surface improved the induction of osteogenic differentiation in comparison to that with the highest stiffness. In conclusion, different to bone marrow derived MSCs, soft ECMs have a superior capacity to support the osteogenic differentiation of DFCs.

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07/30/2011 - Induced in vitro differentiation of neural-like cells from human exfoliated deciduous teeth-derived stem cells.
Int J Dev Biol. 2011;55(2):189-95.

Pediatric Department, School of Dentistry, 2Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Stem cells from human exfoliated deciduous teeth (SHED) are highly proliferative, clonogenic and multipotent stem cells with a neural crest cell origin. Additionally, they can be collected with minimal invasiveness in comparison with other sources of mesenchymal stem cells (MSCs). Therefore, SHED could be a desirable option for potential therapeutic applications. In this study, SHEDs were established from enzyme-disaggregated deciduous dental pulp obtained from 6 to 9 year-old children. The cells had typical fibroblastoid morphology and expressed antigens characteristic of MSCs, STRO1, CD146, CD45, CD90, CD106 and CD166, but not the hematopoietic and endothelial markers, CD34 and CD31, as assessed by FACS analysis. Differentiation assessment revealed a strong osteogenic and adipogenic potential of SHEDs. In order to further evaluate the in vitro differentiation potential of SHED into neural cells, a simple short time growth factor-mediated induction was used. Immunofluorescence staining and flow cytometric analysis revealed that SHED rapidly expressed nestin and b-III tubulin, and later expressed intermediate neural markers. In addition, the intensity and percentages of nestin and b-III tubulin and mature neural markers (PSA-NCAM, NeuN, Tau, TH, or GFAP) increased significantly following treatment. Moreover, RT-PCR and Western blot analyses showed that the neural markers were strongly up-regulated after induction. In conclusion, these results provide evidence that SHED can differentiate into neural cells by the expression of a comprehensive set of genes and proteins that define neural-like cells in vitro. SHED cells might be considered as new candidates for the autologous transplantation of a wide variety of neurological diseases and neurotraumatic injuries.

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07/30/2011 - Pulp tissue from primary teeth: new source of stem cells.
J Appl Oral Sci. 2011 May-Jun;19(3):189-94.

Department of Community Dentistry and Pediatric Dentistry, Dental School, Federal University of Bahia, Salvador, BA, Brazil. p-telles@uol.com.br

SHED (stem cells from human exfoliated deciduous teeth) represent a population of postnatal stem cells capable of extensive proliferation and multipotential differentiation. Primary teeth may be an ideal source of postnatal stem cells to regenerate tooth structures and bone, and possibly to treat neural tissue injury or degenerative diseases. SHED are highly proliferative cells derived from an accessible tissue source, and therefore