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

Congshan Sun; Suraj Kannan; In Young Choi; HoTae Lim; Hao Zhang; Grace S Chen; Nancy Zhang; Seong-Hyun Park; Carlo Serra; Shama R Iyer; Thomas E Lloyd; Chulan Kwon; Richard M Lovering; Su Bin Lim; Peter Andersen; Kathryn R Wagner; Gabsang Lee

doi:10.1016/j.stem.2022.03.004

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.

Authors

Congshan Sun¹, Suraj Kannan², In Young Choi³, HoTae Lim³, Hao Zhang⁴, Grace S Chen⁵, Nancy Zhang⁵, Seong-Hyun Park³, Carlo Serra¹, Shama R Iyer⁶, Thomas E Lloyd⁷, Chulan Kwon², Richard M Lovering⁶, Su Bin Lim⁸, Peter Andersen⁹, Kathryn R Wagner¹⁰, Gabsang Lee¹¹

Affiliations

¹ Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Genetic Muscle Disorders, The Kennedy Krieger Institute, Baltimore, MD 21205, USA.
² Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Biomedical Engineering and Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
³ Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁴ Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
⁵ Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD 21218, USA.
⁶ Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
⁷ Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁸ Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon, 16499, South Korea.
⁹ Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
¹⁰ Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Genetic Muscle Disorders, The Kennedy Krieger Institute, Baltimore, MD 21205, USA. Electronic address: wagnerk@kennedykrieger.org.
¹¹ Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: glee48@jhmi.edu.

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

Abstract

Publication types

MeSH terms

Substances

Grants and funding