Contribution of mesenchymal stem cells in cell based therapies

Abstract

tem cell research evolved as a new hope and has gained tremendous interest in the last two decades to develop new strategies for many of debilitating diseases. Mesenchymal Stem Cells (MSCs) are multipotent cells capable of self-renewal and differentiating into multiple lineages such as osteocytes, adipocytes, chondrocytes, myoblasts, and hepatocytes. MSCs can migrate to the injured tissue and have immunomodulatory effects. Due to these features, MSCs have high therapeutic value in tissue engineering and regenerative medicine. In this thesis, our aim was to investigate the further contribution of the MSCs in different cellular therapies. We used two approaches to accomplish our aim. First, we investigated the possibility of obtaining functional cardiomyocytes from rat MSC within a shorter time period by determining the induction timing of cardiomyocyte differentiation of MSCs. Our data revealed that it is possible to get functional cardiomyocytes from in vitro MSC culture in a shorter time period than previously achieved. This reduction in time may provide emergency cases with access to cell-based therapies that may have previously been unavailable. In the second part of this thesis, we examined in vivo and in vitro effects of a telomerase antagonist, imetelstat (GRN163L) on MSCs. Telomerase activity is essential for the continued growth and survival of malignant cells, therefore inhibition of this activity presents an attractive target for anti-cancer therapy. MSCs also show telomerase activity in maintaining their self-renewal; therefore the effects of telomerase inhibitors on MSCs may be an issue of concern. Our results showed that inhibiting the telomerase activity does not interfere with the self-renewal and differentiation of MSCs under short term in vitro culture conditions.