Human Mesenchymal (Skeletal) Stem Cells: Targets for Skeletal Tissue Regeneration

Moustapha Kassem, MD, PhD

Abstract

Human bone marrow stromal cells (hMSC) contain a population of stem cells called 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: a) approaches to isolated homogenous population of hMSC with stem cell characteristics from the bone marrow using specific criteria, b) 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 “stemmenss” characteristics, c) I will present recent data regarding the molecular control of hMSC differentiation and new factors that maintain hMSC in undifferentiated state and others that 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. d) Finally, I will present the status of some current clinical trials employing MSC for a number of clinical indications.