Highly efficient induction of primate iPS cells by combining RNA transfection and chemical compounds

Genes Cells. 2019 Jul;24(7):473-484. doi: 10.1111/gtc.12702. Epub 2019 Jun 17.

Abstract

Induced pluripotent stem (iPS) cells hold great promise for regenerative medicine and the treatment of various diseases. Before proceeding to clinical trials, it is important to test the efficacy and safety of iPS cell-based treatments using experimental animals. The common marmoset is a new world monkey widely used in biomedical studies. However, efficient methods that could generate iPS cells from a variety of cells have not been established. Here, we report that marmoset cells are efficiently reprogrammed into iPS cells by combining RNA transfection and chemical compounds. Using this novel combination, we generate transgene integration-free marmoset iPS cells from a variety of cells that are difficult to reprogram using conventional RNA transfection method. Furthermore, we show this is similarly effective for human and cynomolgus monkey iPS cell generation. Thus, the addition of chemical compounds during RNA transfection greatly facilitates reprogramming and efficient generation of completely integration-free safe iPS cells in primates, particularly from difficult-to-reprogram cells.

Keywords: ES cell; RNA transfection; chemical compounds; humans; iPS cell; interferon response; mRNA; marmosets; miRNA; primates.

MeSH terms

  • Aged
  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Cellular Reprogramming*
  • Female
  • Fibroblasts / cytology*
  • Fibroblasts / drug effects
  • Fibroblasts / physiology
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / drug effects
  • Induced Pluripotent Stem Cells / physiology
  • Pharmaceutical Preparations / administration & dosage*
  • Platyrrhini
  • RNA / administration & dosage*
  • Transfection / methods*

Substances

  • Pharmaceutical Preparations
  • RNA