Résumé :
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Communication n° 165 Introduction : Myogenic cell transplantation is an approach that could be used to treat muscular disorders such as Duchenne Muscular Dystrophy (DMD). One of the major problems of this method is the poor motogenic capacity of the injected cells. Thus, many injections are required to treat an entire muscle. We have previously demonstrated that the co-injection of growth factors, such as bFGF and IGF-1, with the cells ameliorate considerably their migration. Since a better dispersion was obtained with IGF-1, we hypothesized that the dispersion of human myogenic cells could also be improved by co-injecting them with the mecanogrowth factor (MGF). MGF is an IGF-1 muscle specific isoform. It is expressed in response to physical activity and seems to be responsible for the initial activation of the muscle satellite (stem) cells. Objective : Here, we wanted to study the motogenic capacity of MGF and compare it with IGF-1. Methods : Invasion chambers were used to test the migration capacity of myoblasts treated with both growth factors in vitro. The microtube technique was used to estimate the in vivo dispersion. This test consists of co-injecting the growth factors with PKH-26 labelled (red fluorescence) human cells into a polyethylene microtube which has been placed into the Tibialis anterior muscle of immunodeficient mice. Western blots were also used to elucidate the mechanisms by which MGF could facilitate myogenic cell migration. Results : MGF improved significantly the migration of myogenic cells both in vitro and in vivo. In vitro, two times more cells were able to cross a layer in presence of MGF. Moreover, the migration distance in vivo was 400 µm in the control group and went up to approximately 850 µm in the MGF group. Similar results were obtained with IGF-1. Our results also suggest that MGF promotes the migration of myogenic cells by up-regulating the urokinase plasminogen activator (uPA) and its receptor (uPAR). Conclusions : MGF is a potent motogenic factor that improves the migration of transplanted myogenic cells. The co-injection of MGF with the myoblasts could be a very simple and efficient way to reduce the number of injection needed to treat a DMD patient.
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