1. Chemical-defined and albumin-free generation of human atrial and ventricular myocytes from human pluripotent stem cells
- Author
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Fei Pei, Junjie Jiang, Shuyun Bai, Henghua Cao, Luyang Tian, Ya Zhao, Chuanxiu Yang, Haiheng Dong, and Yue Ma
- Subjects
Human pluripotent stem cells (hPSCs) ,Cardiac subtypes specification ,Albumin ,Antioxidants ,Drugs ,Biology (General) ,QH301-705.5 - Abstract
Most existing culture media for cardiac differentiation of human pluripotent stem cells (hPSCs) contain significant amounts of albumin. For clinical transplantation applications of hPSC-derived cardiomyocytes (hPSC-CMs), culturing cells in an albumin containing environment raises the concern of pathogen contamination and immunogenicity to the recipient patients. In addition, batch-to-batch variation of albumin may cause the inconsistent of hPSC cardiac differentiation. Here, we demonstrated that antioxidants l-ascorbic acid, trolox, N-acetyl-l-cysteine (NAC) and sodium pyruvate could functionally substitute albumin in the culture medium, and formulated an albumin-free, chemical-defined medium (S12 medium). We showed that S12 medium could support efficient hPSC cardiac differentiation with significantly improved reproducibility, and maintained long-term culture of hPSC-CMs. Furthermore, under chemical-defined and albumin-free conditions, human-induced pluripotent stem cells (hiPSCs) were established, and differentiated into highly homogenous atrial and ventricular myocytes in a scalable fashion with normal electrophysiological properties. Finally, we characterized the activity of three typical cardiac ion channels of those cells, and demonstrated that hPSC-derived ventricular cardiomyocytes (hPSC-vCMs) were suitable for drug cardiac safety evaluation. In summary, this simplified, chemical-defined and albumin-free culture medium supports efficient generation and maintaining of hPSC-CMs and facilitates both research and clinical applications of these cells.
- Published
- 2017
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