Xianmei Meng, Ben Van Handel and Ali Nsair
Accepted Abstracts: J Stem Cell Res Ther
Cardiovascular progenitor cells (CVPCs) derived from human pluripotent stem cells (hPSCs) offer great promise for the cell-based therapy of cardiovascular disease (CVD). Here we optimized the differentiation and maintenance conditions in a xeno- and feeder free manner and differentiated hPSCs, including human embryonic stem cell (hESC) lines (H1 and H9) and GMP grade human induced pluripotent stem cell (GMP-hiPSC), into CVPCs. These CVPCs have the ability to be stably and clonally expanded under a xeno- and feeder free manner in vitro. Furthermore, they have the potentials to generate cardiovascular trilineages including cardiomyocytes, smooth muscle cells and endothelial cells in vitro. In conclusion, we obtained the clinical-grade hPSC-derived CVPCs. Our strategies could provide an effective and safe source of cells for myocardial regenerative medicine in clinic. Also, recent data from our group and others has shown that manipulation of the genome of cells in murine hearts can result in direct conversion of these cells into CMs in situ. Using human fibroblasts and compounds that modulate the function of chromatin-modifying enzymes, we have successfully achieved up to 90-fold upregulation of CM structural genes following drug treatment. Moreover, using a similar approach, we have achieved highly efficient conversion to phenotypic endothelial cells as determined by flow cytometry and gene expression. The discovery of such small molecules would provide significant advantages compared to cell-based or gene-based therapies by circumventing commercialization and regulatory challenges.
Xianmei Meng received her PhD in Beijing Institute of Technology, Beijing, China, in the year 2008. Currently, she is an Assistant Project Scientist in University of California, Los Angeles (UCLA)..