The Skeletal Biology Section has focused on stem cells that form hard tissues, in particular, bone marrow stromal stem cells (BMSSCs). Our previous studies have provided evidence for the existence of adult human bone marrow stromal stem cells (BMSSCs). In a recent study, we determined that forced telomerase expression 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). The findings also showed that telomerase can accelerate cell cycle progression from G1-to-S phase by increasing the expression of G1 regulating genes including cyclin D3, cyclin E1, E2F-4, and DP2, associated with hyperphosphorylation of retinoblastoma (pRb), and enhance osteogenic differentiation of BMSSCs, because of the upregulation of CBFA1, osterix, and osteocalcin. While the existence of post-natal stem cells in bone marrow is firmly established, their localization has eluded detection do to the lack of useful definitive markers. We have recently shown that BMSSCs localize to microvasculature in situ, based on their expression of the perivascular markers, STRO-1 and CD146 (MUC-18), using immunofluorescence and magnetic activated cell sorting, similar to what was found for dental pulp stem cells (DPSCs). The finding that different mesenchymal stem cells share a common perivascular niche may have further implications in understanding the factors that regulate the formation of mineralized matrices and other connective tissues.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Intramural Research (Z01)
Project #
1Z01DE000380-20
Application #
6814430
Study Section
(CSDB)
Project Start
Project End
Budget Start
Budget End
Support Year
20
Fiscal Year
2003
Total Cost
Indirect Cost
Name
Dental & Craniofacial Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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