Systemic delivery of human mesenchymal stromal cells combined with IGF-1 enhances muscle functional recovery in LAMA2 dy/2j dystrophic mice.

Abstract

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.

• Authors: Mariane Secco, Carlos Bueno Jr, Natassia M Vieira, Camila Almeida, Mayra Pelatti, Eder Zucconi, Paolo Bartolini, Mariz Vainzof, Elen H Miyabara, Oswaldo K Okamoto, Mayana Zatz
• Journal: Stem cell reviews and reports (Stem Cell Rev Rep) Vol. 9 Issue 1 Pg. 93-109 (Feb 2013) ISSN: 2629-3277 [Electronic] United States
• PMID: 22664740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dystrophin
• Laminin
• laminin alpha 2
• Insulin-Like Growth Factor I

Topics

• Animals
• Cell Differentiation (drug effects)
• Cell- and Tissue-Based Therapy
• Cells, Cultured
• Coculture Techniques
• Dystrophin (biosynthesis)
• Fibrosis (therapy)
• Humans
• Inflammation (therapy)
• Insulin-Like Growth Factor I (pharmacology)
• Laminin (genetics, metabolism)
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells
• Mice
• Muscle Cells (cytology, metabolism)
• Muscle Development (drug effects)
• Muscle Strength (drug effects)
• Muscle, Skeletal (cytology, metabolism)
• Muscular Dystrophy, Animal (therapy)
• Umbilical Cord (cytology)