title: Mesodermal iPSC-derived progenitor cells functionally regenerate cardiac and skeletal muscle.
abstract: Conditions such as muscular dystrophies (MDs) that affect both cardiac and skeletal muscles would benefit from therapeutic strategies that enable regeneration of both of these striated muscle types. Protocols have been developed to promote induced pluripotent stem cells (iPSCs) to differentiate toward cardiac or skeletal muscle; however, there are currently no strategies to simultaneously target both muscle types. Tissues exhibit specific epigenetic alterations; therefore, source-related lineage biases have the potential to improve iPSC-driven multilineage differentiation. Here, we determined that differential myogenic propensity influences the commitment of isogenic iPSCs and a specifically isolated pool of mesodermal iPSC-derived progenitors (MiPs) toward the striated muscle lineages. Differential myogenic propensity did not influence pluripotency, but did selectively enhance chimerism of MiP-derived tissue in both fetal and adult skeletal muscle. When injected into dystrophic mice, MiPs engrafted and repaired both skeletal and cardiac muscle, reducing functional defects. Similarly, engraftment into dystrophic mice of canine MiPs from dystrophic dogs that had undergone TALEN-mediated correction of the MD-associated mutation also resulted in functional striatal muscle regeneration. Moreover, human MiPs exhibited the same capacity for the dual differentiation observed in murine and canine MiPs. The findings of this study suggest that MiPs should be further explored for combined therapy of cardiac and skeletal muscles.
authors.forename: Mattia
authors.initials: M
authors.lastname: Quattrocelli
authors.forename: Melissa
authors.initials: M
authors.lastname: Swinnen
authors.forename: Giorgia
authors.initials: G
authors.lastname: Giacomazzi
authors.forename: Jordi
authors.initials: J
authors.lastname: Camps
authors.forename: Ines
authors.initials: I
authors.lastname: Barthélemy
authors.forename: Gabriele
authors.initials: G
authors.lastname: Ceccarelli
authors.forename: Ellen
authors.initials: E
authors.lastname: Caluwé
authors.forename: Hanne
authors.initials: H
authors.lastname: Grosemans
authors.forename: Lieven
authors.initials: L
authors.lastname: Thorrez
authors.forename: Gloria
authors.initials: G
authors.lastname: Pelizzo
authors.forename: Manja
authors.initials: M
authors.lastname: Muijtjens
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Verfaillie
authors.forename: Stephane
authors.initials: S
authors.lastname: Blot
authors.forename: Stefan
authors.initials: S
authors.lastname: Janssens
authors.forename: Maurilio
authors.initials: M
authors.lastname: Sampaolesi
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004285:Dogs; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000502:physiology*; D009136:Muscular Dystrophies / Q000378:metabolism / Q000628:therapy; D009206:Myocardium; D051381:Rats; D012038:Regeneration