Skeletal stem cells and mechanisms of bone formation
Human bone marrow stromal cells (hMSC) contain a population of stem cells known as skeletal (mesenchymal) stem cells that are capable for differentiation into several mesodermal-type lineages including osteoblasts, adipocytes and chondrocytes. The aim of our research program is to understand the biological characteristics of hMSC so that it is possible to make full use of them in the context of clinical applications. The following topics will be discussed: i) approaches to isolated homogenous population of hMSC with stem cell characteristics from the bone marrow using specific criteria, ii) one major challenge for use of hMSC in clinical application is their limited in vitro proliferative potential and the senescence-associated growth arrest phenotype exhibited by the cells during long-term culture. I will present results from studies in our lab showing that transducing hMSC with human telomerase reverse transcriptase (hTERT) extended the life span of the cells and maintained their stemness characteristics, iii) I will present recent data regarding the molecular control of hMSC differentiation into osteoblastic cells and the identification of new factors that maintain hMSC in undifferentiated state or promote their differentiation into osteoblastic phenotype. I will also present our experience with applying state-of-the-art proteomic approaches to studying the biology of hMSC, iv) Finally, I will present the status of some current clinical trials employing MSC for a number of clinical indications.