Transplantation of PSC-derived myogenic progenitors counteracts disease phenotypes in FSHD mice

Karim Azzag; Darko Bosnakovski; Sudheer Tungtur; Peter Salama; Michael Kyba; Rita C R Perlingeiro

doi:10.1038/s41536-022-00249-0

Transplantation of PSC-derived myogenic progenitors counteracts disease phenotypes in FSHD mice

NPJ Regen Med. 2022 Sep 2;7(1):43. doi: 10.1038/s41536-022-00249-0.

Authors

Karim Azzag¹, Darko Bosnakovski², Sudheer Tungtur¹, Peter Salama¹, Michael Kyba^{2

3}, Rita C R Perlingeiro^{4

5}

Affiliations

¹ Lillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
² Lillehei Heart Institute, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
³ Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA.
⁴ Lillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, MN, USA. perli032@umn.edu.
⁵ Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA. perli032@umn.edu.

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is a genetically dominant progressive myopathy caused by improper silencing of the DUX4 gene, leading to fibrosis, muscle atrophy, and fatty replacement. Approaches focused on muscle regeneration through the delivery of stem cells represent an attractive therapeutic option for muscular dystrophies. To investigate the potential for cell transplantation in FSHD, we have used the doxycycline-regulated iDUX4pA-HSA mouse model in which low-level DUX4 can be induced in skeletal muscle. We find that mouse pluripotent stem cell (PSC)-derived myogenic progenitors engraft in muscle actively undergoing DUX4-mediated degeneration. Donor-derived muscle tissue displayed reduced fibrosis and importantly, engrafted muscles showed improved contractile specific force compared to non-transplanted controls. These data demonstrate the feasibility of replacement of diseased muscle with PSC-derived myogenic progenitors in a mouse model for FSHD, and highlight the potential for the clinical benefit of such a cell therapy approach.

Abstract

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