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Johns Hopkins University School of Medicine

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Cell Stem Cell, 2022 Apr 7;29(4):610-619.e5. | https://doi.org/10.1016/j.stem.2022.03.004 Human pluripotent stem cell-derived myogenic progenitors undergo maturation to quiescent satellite cells upon engraftment

Congshan Sun ^{1 2 11}, Suraj Kannan ^{3 4 5 7}, In Young Choi ^{1 3}, HoTae Lim ^{1 3}, Hao Zhang ⁶, Grace S. Chen ⁸, Nancy Zhang ⁸, Seong-Hyun Park ^{1 3}, Carlo Serra ^{1 2}, Shama R. Iyer ⁹, Thomas E. Lloyd ¹, Chulan Kwon ^{3 4 5 7}, Richard M. Lovering ⁹, Su Bin Lim ¹⁰, Peter Andersen ⁴, Kathryn R. Wagner ^{1 2 12 13 *}, Gabsang Lee ^{1 3 13 14 *}

¹Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
²Center for Genetic Muscle Disorders, The Kennedy Krieger Institute, Baltimore, MD 21205, USA
³Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
⁴Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
⁵Biomedical Engineering and Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
⁶Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
⁷Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
⁸Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD 21218, USA
⁹Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD 21201, USA
¹⁰Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon, 16499, South Korea
¹¹Present address: Vita Therapeutics, Baltimore, MD, USA
¹²Present address: F. Hoffmann La-Roche, Basel, Switzerland
¹³These authors contributed equally
¹⁴Lead contact

*Corresponding author: correspondence to Kathryn R. Wagner or Gabsang Lee

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.

논문정보

형식Research article
게재일2022년 04월 (BRIC 등록일 2023-06-22)
연구진국내+국외 연구진
분야 의약학 > 재생의학

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