ANTIINFLAMMATORY EFFECT OF TRANSFORMING GROWTH-FACTOR-BETA-1 IN MYOBLAST TRANSPLANTATION

Background The inflammatory reaction that occurs during the 5 days aft er transplantation led at 3 days to the death of 70% of injected myobl asts. Use of anti-inflammatory agents appeared to be a possible way to increase myoblast survival. The application of gene transfer techniqu es to cell transplantation offers the potential for the prevention of inflammatory reaction. Methods. In this study, transforming growth fac tor-beta 1 (TGF-beta 1) gene was introduced in myoblasts with a retrov iral vector to permit the secretion of this anti-inflammatory cytokine . Survival of (1) infected myoblasts expressing TGF-beta 1 or (2) norm al myoblasts transplanted with genetically modified cloned myoblasts w as compared with survival of normal myoblasts. Results. Expression of TGF-beta 1 by myoblasts or by cotransplanted cells decreased myoblast mortality after 3 days by roughly 20% (66.0+/-3.0% in control vs. 46.3 +/-4.2% and 46.2+/-5.9%). The increase of myoblast survival by TGF-bet a 1 expression was correlated with a lower polymorphonuclear cell and macrophage infiltration in muscles compared with control. In addition, cytotoxicity of neutrophils against myoblasts was assayed in vitro. T he oxidation of myoblasts by activated neutrophils was decreased after infection of the myoblasts with the TGF-beta 1 retroviral vector. Con clusions. These data demonstrate that the insertion of TGF-beta 1 decr eases inflammatory reaction observed after myoblast transplantation an d thus prolongs their survival.