Chemically Defined Culture Condition for Expansion and Maintenance of Human Pluripotent Stem Cell-DerivedEarly Cardiovascular Progenitor Cells

Cardiovascular progenitor cells (CPCs) are suggested to be invaluablecell sources for a wide range of applications includingexperimental and clinical studies. One of the earliest typeof CPCs is cardiogenic mesodermal cells (CMCs) which cangenerate almost all major types of cardiovascular cells. In orderto benefit from early CPCs, large-scale production of CMCs inan in vitro culture system is required. In this study, we have attemptedto introduce a simple, defined, and reproducible culturesystem for expansion, maintenance, and storage of CMCs derivedfrom human pluripotent stem cells (hPSC). Some signalingmolecules were screened to develop an efficient chemicallydefined culture medium. Cultured CMCs expanded for morethan ۱۰ passages, retained their morphology, gene expressionpattern, chromosomal stability, and in vitro differentiation propensityinto major cardiac lineages and exhibited regenerativepotential when transplanted into the infarcted rat myocardium.We have observed the engraftment of the self-renewed cellsand lack of tumorigenicity after transplantation. This serumandfeeder-free culture system is capable of transformation to acarrier-free suspension culture, which is required for large-scaleproduction of hPSC-derived CMCs. Taken together, our resultsprovide a novel approach for self-renewal and maintenance ofearly CPCs, which is a fundamental step for commercialization,developmental, tissue engineering, and cell-based clinicalstudies.

کلیدواژه ها:

Human Pluripotent Stem Cells ، Early Cardiovascular Progenitor Cells ، Expansion ، Defined Medium