Characterization ex vivo expansion and cardiomyogenic differentiation of human bone marrow derived mesenchymal stem cells

Abstract

Cardiovascular diseases (CVD) are one of the major health problems worldwide and it accounts for one-third of all deaths. It is alarming that, India stands the highest in world for the CVD mortality and occurring in younger age groups thus resulting in tremendous loss of productive working years. Current therapy of heart failure is restricted to pharmacological and for patients with end-stage heart failure treatment options are extremely limited. Therefore, it is essential to develop more effective, less invasive therapeutic strategies. As the self-renewal capacity of adult cardiomyocytes is limited, the development of strategies to regenerate damaged myocardium and improve heart function represents a major challenge. Transplantation of various precursor cells have been attempted for myocardial regeneration, including adult cardiac myocytes, skeletal muscle stem cell, autologous bone marrow stem cells (BMC), immobilized peripheral blood stem cells, embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs). The potential ability of bone marrow derived mesenchymal stem cells (BMSC) to transdifferentiate into cardiomyocytes both in vitro and in vivo are currently being explored for cellular cardiomyoplasty. It has been shown that the methods adopted for isolation, characterization, ex vivo expansion of BMSC and the existing protocols for efficient induction of cardiomyogenic differentiation remain inconsistent. Moreover, the use of BMSCs in cell based therapeutic strategies requires a large number of ex vivo expanded cells that maintain their multilineage differentiation potential under animal serum free conditions are essential. Therefore there is a need to improve the current methods of isolation, characterization, ex vivo expansion and develop protocol for efficient cardiomyogenic differentiation of BMSC. Hence the present study was undertaken to isolate, characterize the BMSCs and evaluate their cardiomyogenic differentiation in animal serum free conditions. The present thesis comprises of five chapters.