Functional Characterization of human iPSC- derived mesenchymal stem cells with cardiomyocyte potential

Professor Tse Hung Fat   (Co-Investigator)

12

2011-02-15

50811

Functional Characterization of human iPSC- derived mesenchymal stem cells with cardiomyocyte potential

cardiac protection, induced pluripotent stem cells, mesenchymal stem cells, myocardiac differentiation, paracrine mechanisms

Cardiovascular Research,Cell Biology

201007176100

Small Project Funding

2010

Completed

The heart has a very limited capacity for repair after myocardial infarction and many cell therapies have been examined in an attempt to improve myocardial repair, cardiac function and long-term survival after severe myocardial infarction. It has been documented that transplantation of human ESC- or iPSC-derived cardiomyocytes led to a very poor survival in host tissues due to a tough environment. Importantly, the different electronic potential of implanted cardiomyocytes frequently resulted in arrhythmia. More recently, mesenchymal stem cells (MSCs), also named multipotent stromal cells have emerged as a promising cell type in the treatment of myocardial and limb ischemia. The MSCs can secrete healing factors, promote new vessel growth and/or differentiate into cardiomyocytes. However, we found the adult tissue-derived MSCs have a limited potential of cardiomyocyte differentiation. We recently have derived a novel MSCs from human induced pluripotent stem cells (iPSC-MSCs). Compare to adult MSCs, we found these early embryonic stage iPSC-MSCs have a greater potential of proliferation and differentiation. Our preliminary studies indicate these iPSC-MSCs can be induced to cardiomyocyte-like with expressing MLC2v, a myosin specific for the ventricle of the mammalian heart. To determine if MLC2v+ cells from iPSC-MSCs have cardiomyocyte functions and have a better therapeutic efficacy in ischemic heart disease ,in this study we aim to isolate and enrich MLC2v+ cells as well as characterize functions of MLC2v+ cells both in vitro and in vivo. Our specific objectives are summarized as following: Objective 1: To enhance differentiation of iPSC-MSC toward cardiomyocyte with expression of MLC2v Objective 2: To purify and enrich MLC2v+ population from iPSC-MSCs as well as characterize functions of MLC2v+ cells in vitro Objective 3: To assess in vivo functions of MLC2v+cells by transplantation of MLC2v+cells into mice with acute heart infarction .