Three-Dimensional Adult Cardiac Extracellular Matrix Promotes Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

摘要: Pluripotent stem cell-derived cardiomyocytes (CMs) have great potential in the development of new therapies for cardiovascular disease. In particular, human induced pluripotent cells (iPSCs) may prove especially advantageous due to their pluripotency, self-renewal potential, and ability create patient-specific cell lines. Unfortunately, CMs are immature, with characteristics more closely resembling fetal than adult CMs, this immaturity has limited use drug screening cell-based therapies. Extracellular matrix (ECM) influences cellular behavior maturation, as does geometry environment-two-dimensional (2D) versus three-dimensional (3D). We therefore tested hypothesis that native cardiac ECM 3D cultures might enhance maturation iPSC-derived vitro. demonstrate was enhanced when were seeded into a scaffold, compared 2D culture. promoted increased expression calcium-handling genes, Junctin, CaV1.2, NCX1, HCN4, SERCA2a, Triadin, CASQ2. Consistent this, we find show calcium signaling (amplitude) kinetics (maximum upstroke downstroke) 2D. Cells culture also responsive caffeine, likely reflecting an availability sarcoplasmic reticulum. Taken together, these studies provide novel strategies maturing applications transplantation treat heart