Human pluripotent stem cell-derived myogenic progenitors undergo maturation to quiescent satellite cells upon engraftment

Cell Stem Cell. 2022 Apr 7;29(4):610-619.e5. doi: 10.1016/j.stem.2022.03.004.

Abstract

Human pluripotent stem cell (hPSC)-derived myogenic progenitor cell (MPC) transplantation is a promising therapeutic approach for a variety of degenerative muscle disorders. Here, using an MPC-specific fluorescent reporter system (PAX7::GFP), we demonstrate that hPSC-derived MPCs can contribute to the regeneration of myofibers in mice following local injury and in mice deficient of dystrophin (mdx). We also demonstrate that a subset of PAX7::GFP MPCs engraft within the basal lamina of regenerated myofibers, adopt a quiescent state, and contribute to regeneration upon reinjury and in mdx mouse models. This subset of PAX7::GFP MPCs undergo a maturation process and remodel their molecular characteristics to resemble those of late-stage fetal MPCs/adult satellite cells following in vivo engraftment. These in-vivo-matured PAX7::GFP MPCs retain a cell-autonomous ability to regenerate and can repopulate in the niche of secondary recipient mice, providing a proof of principle for future hPSC-based cell therapy for muscle disorders.

Keywords: Duchenne muscular dystrophy; mdx mouse; pluripotent stem cells; quiescent stem cells; skeletal muscle stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Dystrophin
  • Humans
  • Mice
  • Mice, Inbred mdx
  • Muscle Development
  • Muscle, Skeletal
  • Myoblasts
  • Pluripotent Stem Cells*
  • Satellite Cells, Skeletal Muscle*
  • Stem Cell Transplantation

Substances

  • Dystrophin