Systemic delivery of human mesenchymal stromal cells combined with IGF-1 enhances muscle functional recovery in LAMA2 dy/2j dystrophic mice.
The combination of cell therapy with growth factors could be a useful approach to treat progressive muscular dystrophies. Here, we demonstrate, for the first time, that IGF-1 considerably enhances the myogenesis of human umbilical cord (UC) mesenchymal stromal cells (MSCs) in vitro and that IGF-1 enhances interaction and restoration of dystrophin expression in co-cultures of MSCs and muscle cells from Duchenne patients. In vivo studies showed that human MSCs were able to reach the skeletal muscle of LAMA2(dy/2j) dystrophic mice, through systemic delivery, without immunosuppression. Moreover, we showed, for the first time, that IGF-1 injected systemically together with MSCs markedly reduced muscle inflammation and fibrosis, and significantly improved muscle strength in dystrophic mice. Our results suggest that a combined treatment with IGF-1 and MSCs enhances efficiency of muscle repair and, therefore, should be further considered as a potential therapeutic approach in muscular dystrophies.
Human Genome Research Center, Department of Genetic and Evolutionary Biology, Institute of Biosciences, São Paulo, Brazil.
Mariane
M
Secco
Carlos
C
Bueno
Natassia M
NM
Vieira
Camila
C
Almeida
Mayra
M
Pelatti
Eder
E
Zucconi
Paolo
P
Bartolini
Mariz
M
Vainzof
Elen H
EH
Miyabara
Oswaldo K
OK
Okamoto
Mayana
M
Zatz
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D018920:Coculture Techniques; D016189:Dystrophin / Q000096:biosynthesis; D005355:Fibrosis / Q000628:therapy; D006801:Humans; D007249:Inflammation / Q000628:therapy; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D051379:Mice; D032342:Muscle Cells / Q000166:cytology / Q000378:metabolism; D024510:Muscle Development / Q000187:drug effects*; D053580:Muscle Strength / Q000187:drug effects; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D009137:Muscular Dystrophy, Animal / Q000628:therapy*; D014470:Umbilical Cord / Q000166:cytology
D016189:Dystrophin; D007797:Laminin; C102645:laminin alpha 2; D007334:Insulin-Like Growth Factor I