Biomedical subjects

Songtao Shi

Publications and source records attributed to Songtao Shi.

24 records · Page 2Linked to original sources

PubMed2003

SHED: stem cells from human exfoliated deciduous teeth.

To isolate high-quality human postnatal stem cells from accessible resources is an important goal for stem-cell research. In this study we found that exfoliated human deciduous tooth contains multipotent stem cells [stem cells from human exfoliated deciduous teeth (SHED)]. SHED were identified to be a population of highly proliferative, clonogenic cells capable of differentiating into a variety of cell types including neural cells, adipocytes, and odontoblasts. After in vivo transplantation, SHED were found to be able to induce bone formation, generate dentin, and survive in mouse brain along with expression of neural markers. Here we show that a naturally exfoliated human organ contains a population of stem cells that are completely different from previously identified stem cells. SHED are not only derived from a very accessible tissue resource but are also capable of providing enough cells for potential clinical application. Thus, exfoliated teeth may be an unexpected unique resource for stem-cell therapies including autologous stem-cell transplantation and tissue engineering.

Animals↗

PubMed2003

Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp.

Mesenchymal stem cell populations have previously been identified in adult bone marrow and dental pulp that are capable of regenerating the bone marrow and dental pulp microenvironments, respectively. Here we show that these stem cell populations reside in the microvasculature of their tissue of origin. Human bone marrow stromal stem cells (BMSSCs) and dental pulp stem cells (DPSCs) were isolated by immunoselection using the antibody, STRO-1, which recognizes an antigen on perivascular cells in bone marrow and dental pulp tissue. Freshly isolated STRO-1 positive BMSSCs and DPSCs were tested for expression of vascular antigens known to be expressed by endothelial cells (von Willebrand factor, CD146), smooth muscle cells, and pericytes (alpha-smooth muscle actin, CD146), and a pericyte-associated antigen (3G5), by immunohistochemistry, fluorescence-activated cell sorting (FACS), and/or immunomagnetic bead selection. Both BMSSCs and DPSCs lacked expression of von Willebrand factor but were found to be positive for alpha-smooth muscle actin and CD146. Furthermore, the majority of DPSCs expressed the pericyte marker, 3G5, while only a minor population of BMSSCs were found to be positive for 3G5. The finding that BMSSCs and DPSCs both display phenotypes consistent with different perivascular cell populations, regardless of their diverse ontogeny and developmental potentials, may have further implications in understanding the factors that regulate the formation of mineralized matrices and other associated connective tissues.

Adult↗

PubMed2003

Telomerase accelerates osteogenesis of bone marrow stromal stem cells by upregulation of CBFA1, osterix, and osteocalcin.

Telomerase activity can prevent telomere shortening and replicative senescence in human somatic cells. We and others have previously demonstrated that forced expression of telomerase in human bone marrow stromal stem cells (BMSSCs) was able to extend their life-span and enhance their bone-forming capability, without inducing malignant transformation. In this study, we determined that telomerase was able to accelerate calcium accumulation of human BMSSCs under osteogenic inductive conditions. Similarly, xenogeneic transplantation of telomerase-expressing BMSSCs (BMSSC-Ts) yielded ectopic bone formation at 2 weeks post-transplantation, 2-4 weeks earlier than typically seen with BMSSCs transfected with empty vector (BMSSC-Cs). Low-density DNA array analysis revealed that telomerase activity increases the expression of G1 regulating genes including cyclin D3, cyclin E1, E2F-4, and DP2, associated with hyperphosphorylation of retinoblastoma (pRb), leading to the extended proliferative capacity of BMSSC-Ts. Importantly, BMSSC-T transplants showed a higher number of human osteogenic cells at 8 weeks post transplantation compared with the BMSSC-C transplants, coupled with a significantly increased osteogenic capacity. One possible mechanism leading to accelerated osteogenesis by BMSSC-Ts may be attributed, at least in part, to the upregulation of the important osteogenic genes such as CBFA1, osterix, and osteocalcin in vitro. Taken together, these findings show that telomerase can accelerate cell cycle progression from G1-to-S phase and enhance osteogenic differentiation of BMSSCs, because of the upregulation of CBFA1, osterix, and osteocalcin.

Alu Elements↗

PubMed2002

Bone formation by human postnatal bone marrow stromal stem cells is enhanced by telomerase expression.

Human postnatal bone marrow stromal stem cells (BMSSCs) have a limited life-span and progressively lose their stem cell properties during ex vivo expansion. Here we report that ectopic expression of human telomerase reverse transcriptase (hTERT) in BMSSCs extended their life-span and maintained their osteogenic potential. In xenogenic transplants, hTERT-expressing BMSSCs (BMSSC-Ts) generated more bone tissue, with a mineralized lamellar bone structure and associated marrow, than did control BMSSCs. The enhanced bone-forming ability of BMSSC-Ts was correlated with a higher and sustained expression of the early pre-osteogenic stem cell marker STRO-1, indicating that telomerase expression helped to maintain the osteogenic stem cell pool during ex vivo expansion. These results show that telomerase expression can overcome critical technical barriers to the ex vivo expansion of BMSSCs, and suggest that telomerase therapy may be a useful strategy for bone regeneration and repair.

Adult↗

PubMed2002

Age-related osteoporosis in biglycan-deficient mice is related to defects in bone marrow stromal cells.

Biglycan (bgn) is an extracellular matrix proteoglycan that is enriched in bone and other skeletal connective tissues. Previously, we generated bgn-deficient mice and showed that they developed age-dependent osteopenia. To identify the cellular events that might contribute to this progressive osteoporosis, we measured the number of osteogenic precursors in the bone marrow of normal and mutant mice. The number of colonies, indicative of the colony-forming unit potential of fibroblasts (CFU-F), gradually decreased with age. By 24 weeks of age, colony formation in the bgn knockout (KO) mice was significantly more reduced than that in the wild type (wt) mice. This age-related reduction was consistent with the extensive osteopenia previously shown by X-ray analysis and histological examination of 24-week-old bgn KO mice. Because bgn has been shown previously to bind and regulate transforming growth factor beta (TGF-beta) activity, we also asked whether this growth factor would affect colony formation. TGF-beta treatment significantly increased the size of the wt colonies. In contrast, TGF-beta did not significantly influence the size of the bgn colonies. An increase in apoptosis in bgn-deficient bone marrow stromal cells (BMSCs) was observed also. The combination of decreased proliferation and increased apoptosis, if it occurred in vivo, would lead to a deficiency in the generation of mature osteoblasts and would be sufficient to account for the osteopenia developed in the bgn KO mice. The bgn KO mice also were defective in the synthesis of type I collagen messenger RNA (mRNA) and protein. This result supports the suggestion that the composition of the extracellular matrix may be regulated by specific matrix components including bgn.

Animals↗

PubMedDate not supplied

Investigation of multipotent postnatal stem cells from human periodontal ligament.

BACKGROUND: Periodontal diseases that lead to the destruction of periodontal tissues--including periodontal ligament (PDL), cementum, and bone--are a major cause of tooth loss in adults and are a substantial public-health burden worldwide. PDL is a specialised connective tissue that connects cementum and alveolar bone to maintain and support teeth in situ and preserve tissue homoeostasis. We investigated the notion that human PDL contains stem cells that could be used to regenerate periodontal tissue. METHODS: PDL tissue was obtained from 25 surgically extracted human third molars and used to isolate PDL stem cells (PDLSCs) by single-colony selection and magnetic activated cell sorting. Immunohistochemical staining, RT-PCR, and northern and western blot analyses were used to identify putative stem-cell markers. Human PDLSCs were transplanted into immunocompromised mice (n=12) and rats (n=6) to assess capacity for tissue regeneration and periodontal repair. Findings PDLSCs expressed the mesenchymal stem-cell markers STRO-1 and CD146/MUC18. Under defined culture conditions, PDLSCs differentiated into cementoblast-like cells, adipocytes, and collagen-forming cells. When transplanted into immunocompromised rodents, PDLSCs showed the capacity to generate a cementum/PDL-like structure and contribute to periodontal tissue repair. INTERPRETATION: Our findings suggest that PDL contains stem cells that have the potential to generate cementum/PDL-like tissue in vivo. Transplantation of these cells, which can be obtained from an easily accessible tissue resource and expanded ex vivo, might hold promise as a therapeutic approach for reconstruction of tissues destroyed by periodontal diseases.

Adult↗