Skeletal muscle regeneration via the chemical induction and expansion of myogenic stem cells in situ or in vitro

Jun Fang; Junren Sia; Jennifer Soto; Pingping Wang; LeeAnn K Li; Yuan-Yu Hsueh; Raymond Sun; Kym Francis Faull; James G Tidball; Song Li

doi:10.1038/s41551-021-00696-y

Skeletal muscle regeneration via the chemical induction and expansion of myogenic stem cells in situ or in vitro

Nat Biomed Eng. 2021 Aug;5(8):864-879. doi: 10.1038/s41551-021-00696-y. Epub 2021 Mar 18.

Authors

Jun Fang^#^{1

2}, Junren Sia^#³, Jennifer Soto^{1

2}, Pingping Wang^{1

4}, LeeAnn K Li^{1

5}, Yuan-Yu Hsueh^{1

6}, Raymond Sun³, Kym Francis Faull^{7

8}, James G Tidball^{9

10

11}, Song Li^{12

13}

Affiliations

¹ Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA.
² Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
³ Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
⁴ Beijing Key Laboratory of Bioelectromagnetism, Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing, China.
⁵ David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁶ Division of Plastic Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁷ Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁸ Pasarow Mass Spectrometry Laboratory, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA.
⁹ Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
¹⁰ Molecular, Cellular & Integrative Physiology Program, University of California, Los Angeles, Los Angeles, CA, USA.
¹¹ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
¹² Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA. songli@ucla.edu.
¹³ Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. songli@ucla.edu.

^# Contributed equally.

Abstract

Muscle loss and impairment resulting from traumatic injury can be alleviated by therapies using muscle stem cells. However, collecting sufficient numbers of autologous myogenic stem cells and expanding them efficiently has been challenging. Here we show that myogenic stem cells (predominantly Pax7⁺ cells)-which were selectively expanded from readily obtainable dermal fibroblasts or skeletal muscle stem cells using a specific cocktail of small molecules and transplanted into muscle injuries in adult, aged or dystrophic mice-led to functional muscle regeneration in the three animal models. We also show that sustained release of the small-molecule cocktail in situ through polymer nanoparticles led to muscle repair by inducing robust activation and expansion of resident satellite cells. Chemically induced stem cell expansion in vitro and in situ may prove to be advantageous for stem cell therapies that aim to regenerate skeletal muscle and other tissues.

Publication types

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

MeSH terms

Animals
Cellular Reprogramming / drug effects
Colforsin / pharmacology
Culture Media / chemistry
Culture Media / pharmacology
Fibroblasts / cytology
Fibroblasts / metabolism
Mice
Muscle, Skeletal / physiology*
Muscular Diseases / therapy
Nanoparticles / chemistry
PAX7 Transcription Factor / metabolism
Polymers / chemistry
Regeneration*
Satellite Cells, Skeletal Muscle / cytology*
Satellite Cells, Skeletal Muscle / metabolism
Satellite Cells, Skeletal Muscle / transplantation
Stem Cell Transplantation
Stem Cells / cytology
Stem Cells / metabolism
Valproic Acid / pharmacology

Substances

Culture Media
PAX7 Transcription Factor
Polymers
Colforsin
Valproic Acid

Associated data

figshare/10.6084/m9.figshare.13049690.v1

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding