2013 - CTS 2013 Congress
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Oral Communications 9
20.5 - Intra-arterial delivery of myoblasts to skeletal muscles in primates
Presenter: Daniel, Skuk, Quebec, Canada
Authors: Daniel Skuk1, Marlyne Goulet1, Jacques P. Tremblay1
Intra-arterial delivery of myoblasts to skeletal muscles in primates
Daniel Skuk1, Marlyne Goulet1, Jacques P. Tremblay1
1Neurosciences Division – Human Genetics, CHUQ Research Center, Quebec, QC, Canada
Background. The intramuscular transplantation of myogenic cells presents several constraints and the intravascular route seems to be a better strategy of cell delivery. However, so far this route seems to work only with special cells such as mesoangioblasts and CD133+ cells. Experiments of intravascular delivery of myoblasts in mice produced limited results, but mice are not a good reference for human extrapolation given important differences in the myoblast transplantation biology. The close phylogenetic relationship between humans and macaques provides the best anatomical, cell culture, antigenic and immunological similarities for preclinical research in this field. Thus, we decide to test the intra-arterial (IA) allotransplantation of myoblasts in macaques.
Methods. Experiments were conducted in adult cynomolgus monkeys. ß-galactosidase (ß-Gal)-labeled myoblasts were proliferated in vitro, resuspended in heparinized saline and injected slowly in one femoral artery. Regions of muscles both in the leg ipsilateral to the injection and other limbs were damaged with a 27G needle (100 parallel penetrations per cm2) or by electroporation. Monkeys were submitted to euthanasia 1 hour or 1 day (n = 3) and 3-4 weeks (n = 3) post-transplantation. Monkeys were immunosuppressed with tacrolimus in the long-term follow-up. Samples were taken in different skeletal muscles and organs (lungs, heart, brain, cerebellum, gut, liver and spleen). Samples were frozen in liquid nitrogen and sections were made in a cryostat to be analyzed by histology.
Results. Most myoblasts were retained mainly in the capillaries of the skeletal muscles of the leg ipsilateral to the injection. Some small accumulations were observed in arterioles. No histological evidences of micro-infarcts were observed. Scarce ß-Gal+ cells were observed in the lungs 1 hour after transplantation. No ß-Gal+ cells were observed in other organs or other muscles. ß-Gal+ myofibers were observed 3-4 weeks after transplantation in muscle biopsies of the ipsilateral leg to the injection, in the regions damaged at the time of the cell injection.
Conclusions. Myoblasts can be safely delivered by the femoral artery in primates. Most of these myoblasts are retained in capillaries between myofibers. Myoblast retention in capillaries might be due to a mechanism of plugging, as is frequent in the case of leukocytes, rather than to specific homing. These myoblasts are capable to fuse with regenerating myofibers. Further experiments are needed to know the potentiality of the IA delivery of myoblasts in humans.
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