Skeletal muscle perfusion and stem cell delivery in muscle disorders using intra-femoral artery canulation in mice.
Muscular dystrophies are among major inherited muscle disorders characterized by progressive muscle damage and fibrosis with no definitive cure. Recently, gene or cell based therapies have been developed to restore the missing gene expression or replace the damaged tissues. In order to test the efficiency of these therapies in mice models of muscular dystrophies, the arterial route of delivery is very advantageous as it provides uniform muscle exposure to the therapeutic agents or cells. Although there are few reports of arterial delivery of the therapeutic agents or cells in mice, there is no in-depth description and evaluation of its efficacy in perfusion of downstream muscles. This study is aimed to develop a practical method for intra-femoral artery perfusion in mice and to evaluate perfusion efficiency using near-infrared-fluorescence (NIRF) imaging as well as histology following stem cell delivery. Our results provide a practical guide to perform this delicate method in mice. By using a sensitive fluorescent dye, different muscle groups of the hindlimb have been evaluated for proper perfusion. As the final step, we have validated the efficiency of arterial cell delivery into muscles using human iPS-derived myogenic cells in an immunodeficient mouse model for Duchenne muscular dystrophy (NSG-mdx(4cv)).
Center for Stem Cell and Regenerative Medicine (CSCRM), Brown Foundation Institute of Molecular Medicine (IMM), University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Nadine
N
Matthias
Center for Stem Cell and Regenerative Medicine (CSCRM), Brown Foundation Institute of Molecular Medicine (IMM), University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Samuel D
SD
Hunt
Center for Stem Cell and Regenerative Medicine (CSCRM), Brown Foundation Institute of Molecular Medicine (IMM), University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Jianbo
J
Wu
Center for Stem Cell and Regenerative Medicine (CSCRM), Brown Foundation Institute of Molecular Medicine (IMM), University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Electronic address: radbod.darabi@uth.tmc.edu.
Radbod
R
Darabi
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D016189:Dystrophin / Q000172:deficiency; D005263:Femoral Artery / Q000378:metabolism / Q000601:surgery*; D006614:Hindlimb; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D009137:Muscular Dystrophy, Animal / Q000628:therapy*; D020388:Muscular Dystrophy, Duchenne / Q000628:therapy*; D010477:Perfusion; D033581:Stem Cell Transplantation
D016189:Dystrophin
IA delivery; Intra-femoral artery perfusion; Muscular dystrophies; Skeletal muscle; Stem cell therapy