Anti-inflammatory effect of transforming growth factor-beta1 in myoblast transplantation.
BACKGROUND
The inflammatory reaction that occurs during the 5 days after transplantation led at 3 days to the death of 70% of injected myoblasts. Use of anti-inflammatory agents appeared to be a possible way to increase myoblast survival. The application of gene transfer techniques to cell transplantation offers the potential for the prevention of inflammatory reaction.


METHODS
In this study, transforming growth factor-beta1 (TGF-beta1) gene was introduced in myoblasts with a retroviral vector to permit the secretion of this anti-inflammatory cytokine. Survival of (1) infected myoblasts expressing TGF-beta1 or (2) normal myoblasts transplanted with genetically modified cloned myoblasts was compared with survival of normal myoblasts.


RESULTS
Expression of TGF-beta1 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-beta1 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. The oxidation of myoblasts by activated neutrophils was decreased after infection of the myoblasts with the TGF-beta1 retroviral vector.


CONCLUSIONS
These data demonstrate that the insertion of TGF-beta1 decreases inflammatory reaction observed after myoblast transplantation and thus prolongs their survival.
Merly
F
F
Centre de Recherche en Neurobiologie, Université Laval, Hôpital de l'Enfant-Jésus, Québec, Canada.
Huard
C
C
Asselin
I
I
Robbins
P D
PD
Tremblay
J P
JP
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007958:Leukocyte Count; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000637:transplantation*; D009132:Muscles / Q000473:pathology; D009504:Neutrophils; D009195:Peroxidase / Q000378:metabolism; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D009195:Peroxidase