PUBLISHED RESEARCH 2005

BACKGROUND: Bone marrow mesenchymal stem cells (MSCs) are currently being investigated in preclinical and clinical settings because of their multipotent differentiative capacity or, alternatively, their immunosuppressive function. The aim of this study was to evaluate dental pulp (DP) as a potential source of MSCs instead of bone marrow (BM).
METHODS: Flow cytometric analysis showed that DP-MSCs and BM-MSCs were equally SH2, SH3, SH4, CD29 and CD 166 positive. The in vitro proliferative kinetics of MSCs were measured by 3H-thymidine incorporation uptake. The immunosuppressive function of MSCs was then tested by coculturing PHA-stimulated allogeneic T cells with or without MSCs for 3 days.
RESULTS: BM-MSCs could be differentiated in vitro into osteogenic, chondrogenic and adipogenic lineages. DP-MSCs showed osteogenic and adipocytic differentiation, but did not differentiate into chondrocytes. Although DP-MSCs grow rapidly in vitro between day 3 and day 8 of culture and then decrease their proliferation by day 15, BM-MSCs have a stable and continuous proliferation over the same period of time. The addition of DP-MSCs or BM-MSCs resulted in 91 +/- 4% and 75 +/- 3% inhibition of T cell response, respectively, assessed by a 3H-thymidine assay.
CONCLUSIONS: Dental pulp is an easily accessible and efficient source of MSCs, with different kinetics and differentiation potentialities from MSCs as isolated from the bone marrow. The rapid proliferative capacity together with the immunoregulatory characteristics of DP-MSCs may prompt future studies aimed at using these cells in the treatment or prevention of T-cell alloreactivity in hematopoietic or solid organ allogeneic transplantation.

Abstract: Caries, pulpitis, and apical periodontitis increase health care costs and attendant loss of economic productivity. They ultimately result in premature tooth loss and therefore diminishing the quality of life. Advances in vital pulp therapy with pulp stem/progenitor cells might give impetus to regenerate dentin-pulp complex without the removal of the whole pulp. Tissue engineering is the science of design and manufacture of new tissues to replace lost parts because of diseases including cancer and trauma. The three key ingredients for tissue engineering are signals for morphogenesis, stem cells for responding to morphogens and the scaffold of extracellular matrix. In preclinical studies cell therapy and gene therapy have been developed for many tissues and organs such as bone, heart, liver, and kidney as a means of delivering growth factors, cytokines, or morphogens with stem/progenitor cells in a scaffold to the sites of tissue injury to accelerate and/or induce a natural biological regeneration. The pulp tissue contains stem/progenitor cells that potentially differentiate into odontoblasts in response to bone morphogenetic proteins (BMPs). There are two strategies to regenerate dentin. First, is in vivo therapy, where BMP proteins or BMP genes are directly applied to the exposed or amputated pulp. Second is ex vivo therapy and consists of isolation of stem/progenitor cells from pulp tissue, differentiation into odontoblasts with recombinant BMPs or BMP genes and finally transplanted autogenously to regenerate dentin. This review is focused on the recent progress in this area and discusses the barriers and challenges for clinical utility in endodontics.

Abstract: The evolving challenge of managing patients with congestive heart failure is the need to develop new therapeutic strategies. The cellular, molecular, and genetic approaches investigated aim to reinforce the weak, failing heart muscle while restoring its functional potential. This approach is principally cellular therapy (i.e. cellular cardiomyoplasty), the preferred therapeutic choice because of its clinical applicability and regenerative capacity. Different stem cells: bone marrow cells, skeletal and smooth muscle cells, vascular endothelial cells, mesothelial cells, adipose tissue stroma cells, dental stem cells, and embryonic and fetal cells, have been proposed for regenerative medicine and biology. Stem cell mobilization with G-CSF cytokine was also proposed as a single therapy for myocardial infarction. We investigated the association of cell therapy with electrostimulation (dynamic cellular cardiomyoplasty), the use of autologous human serum for cell cultures, and a new catheter for simultaneous infarct detection and cell delivery. Our team conducted cell-based myogenic and angiogenic clinical trials for chronic ischemic heart disease. Cellular cardiomyoplasty constitutes a new approach for myocardial regeneration; the ultimate goal is to avoid the progression of ventricular remodeling and heart failure for patients presenting with ischemic and non-ischemic cardiomyopathies.

OBJECTIVE: To isolate and cultivate human dental pulp stem cells (DPSCs).
METHODS: Pulp tissue was removed from healthy young human teeth extracted for orthodontic purposes. The pulp was digested by Type I collagenase and dispase. Then single-cell suspensions were obtained by filter and cultivated. The clones were identified by expression of STRO-1. Under the conditions of inducement, clones were identified by activity of alkaline phosphatase (ALP), formation of mineralized nodule and expression of dentin sialoprotein (DSP), and by Oil Red-O dyeing and expressing of PPARr2.
RESULTS: The clones had positive expression of STRO-1. When stimulated to differentiation, these cells took on dramatically high activity of ALP, had the ability of mineralization and expressed DSP. These cells also had ability to trans-differentiate into adipocytes.
CONCLUSION: There are stem cells in human dental pulp tissues, which can be isolated and cultivated.

Abstract: The dental follicle is an ectomesenchymal tissue surrounding the developing tooth germ. It is believed that this tissue contains stem cells and lineage committed progenitor cells or precursor cells (PCs) for cementoblasts, periodontal ligament cells, and osteoblasts. In this study, we report the isolation of PCs derived from dental follicle of human third molar teeth. These fibroblast-like, colony forming and plastic adherent cells expressed putative stem cell markers Notch-1 and Nestin. We compared gene expressions of PCs, human mesenchymal stem cells (hMSCs), periodontal ligament cells (PDL-cells) and osteoblasts (MG63) for delimitation of PCs. Interestingly, PCs expressed higher amounts of insulin-like growth factor-2 (IGF-2) transcripts than hMSCs. Differentiation capacity was demonstrated under in vitro conditions for PCs. Long-term cultures with dexamethasone produced compact calcified nodules or appeared as plain membrane structures of different dimensions consisting of a connective tissue like matrix encapsulated by a mesothelium-like cellular structure. PCs differentially express osteocalcin (OCN) and bone sialoprotein (BS) after transplantation in immunocompromised mice but without any sign of cementum or bone formation. Therefore, our results demonstrate that cultured PCs are unique undifferentiated lineage committed cells residing in the periodontium prior or during tooth eruption.