title: Slowing down differentiation of engrafted human myoblasts into immunodeficient mice correlates with increased proliferation and migration.
abstract: We have used a model of xenotransplantation in which human myoblasts were transplanted intramuscularly into immunodeficient Rag2(-/-)γC(-/-) mice, in order to investigate the kinetics of proliferation and differentiation of the transplanted cells. After injection, most of the human myoblasts had already differentiated by day 5. This differentiation correlated with reduction in proliferation and limited migration of the donor cells within the regenerating muscle. These results suggest that the precocious differentiation, already detected at 3 days postinjection, is a limiting factor for both the migration from the injection site and the participation of the donor cells to muscle regeneration. When we stimulated in vivo proliferation of human myoblasts, transplanting them in a serum-containing medium, we observed 5 days post-transplantation a delay of myogenic differentiation and an increase in cell numbers, which colonized a much larger area within the recipient's muscle. Importantly, these myoblasts maintained their ability to differentiate, since we found higher numbers of myofibers seen 1 month postengraftment, as compared to controls. Conceptually, these data suggest that in experimental myoblast transplantation, any intervention upon the donor cells and/or the recipient's microenvironment aimed at enhancing proliferation and migration should be done before differentiation of the implanted cells, e.g., day 3 postengraftment.
authors.affiliation: Thérapie des maladies du muscle strié/Institut de Myologie UM76, Université Pierre et Marie Curie, INSERM-U974; CNRS-UMR7215, Paris, France.
authors.forename: Ingo
authors.initials: I
authors.lastname: Riederer
authors.forename: Elisa
authors.initials: E
authors.lastname: Negroni
authors.forename: Maximilien
authors.initials: M
authors.lastname: Bencze
authors.forename: Annie
authors.initials: A
authors.lastname: Wolff
authors.forename: Ahmed
authors.initials: A
authors.lastname: Aamiri
authors.forename: James P
authors.initials: JP
authors.lastname: Di Santo
authors.forename: Suse D
authors.initials: SD
authors.lastname: Silva-Barbosa
authors.forename: Gillian
authors.initials: G
authors.lastname: Butler-Browne
authors.forename: Wilson
authors.initials: W
authors.lastname: Savino
authors.forename: Vincent
authors.initials: V
authors.lastname: Mouly
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints; D002454:Cell Differentiation; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D018482:Muscle, Skeletal / Q000502:physiology; D032446:Myoblasts / Q000166:cytology* / Q000637:transplantation*; D061251:Primary Cell Culture; D012038:Regeneration / Q000502:physiology; D014183:Transplantation, Heterologous