Anti-inflammatory effect of transforming growth factor-β1 in myoblast transplantation

Franck Merly, Christine Huard, Isabelle Asselin, Paul D. Robbins, Jacques P. Tremblay

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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-β1 (TGF-β1) 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-β1 or (2) normal myoblasts transplanted with genetically modified cloned myoblasts was compared with survival of normal myoblasts. Results. Expression of TGF-β1 by myoblasts or by cotransplanted calls decreased myoblast mortality after 3 days by roughly 20% (66.0±3.0% in control vs. 46.3±4.2% and 462±5.9%). The increase of myoblast survival by TGF-β1 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-β1 retroviral vector. Conclusions. These data demonstrate that the insertion of TGF-β1 decreases inflammatory reaction observed after myoblast transplantation and thus prolongs their survival.

Original languageEnglish (US)
Pages (from-to)793-799
Number of pages7
JournalTransplantation
Volume65
Issue number6
DOIs
StatePublished - Mar 27 1998
Externally publishedYes

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