Abstract:
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.
journal_name
Transplantationjournal_title
Transplantationauthors
Merly F,Huard C,Asselin I,Robbins PD,Tremblay JPdoi
10.1097/00007890-199803270-00005subject
Has Abstractpub_date
1998-03-27 00:00:00pages
793-9issue
6eissn
0041-1337issn
1534-6080journal_volume
65pub_type
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