Amniotic fluid stem cells restore the muscle cell niche in a HSA-Cre, Smn(F7/F7) mouse model.
Mutations in the survival of motor neuron gene (SMN1) are responsible for spinal muscular atrophy, a fatal neuromuscular disorder. Mice carrying a homozygous deletion of Smn exon 7 directed to skeletal muscle (HSA-Cre, Smn(F7/F7) mice) present clinical features of human muscular dystrophies for which new therapeutic approaches are highly warranted. Herein we demonstrate that tail vein transplantation of mouse amniotic fluid stem (AFS) cells enhances the muscle strength and improves the survival rate of the affected animals. Second, after cardiotoxin injury of the Tibialis Anterior, only AFS-transplanted mice efficiently regenerate. Most importantly, secondary transplants of satellite cells (SCs) derived from treated mice show that AFS cells integrate into the muscle stem cell compartment and have long-term muscle regeneration capacity indistinguishable from that of wild-type-derived SC. This is the first study demonstrating the functional and stable integration of AFS cells into the skeletal muscle, highlighting their value as cell source for the treatment of muscular dystrophies.
Department of Pediatrics and Pediatric Surgery, University of Padova, Padova, Italy.
Martina
M
Piccoli
Chiara
C
Franzin
Enrica
E
Bertin
Luca
L
Urbani
Bert
B
Blaauw
Andrea
A
Repele
Elisa
E
Taschin
Angelo
A
Cenedese
Giovanni Franco
GF
Zanon
Isabelle
I
André-Schmutz
Antonio
A
Rosato
Judith
J
Melki
Marina
M
Cavazzana-Calvo
Michela
M
Pozzobon
Paolo
P
De Coppi
D000653:Amniotic Fluid / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000166:cytology* / Q000503:physiopathology; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D011897:Random Allocation; D055153:Stem Cell Niche / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics
C526472:Smn1 protein, mouse; D055533:Survival of Motor Neuron 1 Protein