COMPLEMENT DEPOSITION AND CELL-DEATH AFTER MYOBLAST TRANSPLANTATION

One of the problems limiting myoblast transplantation (MT) is the earl y death of the transplanted cells. Because complement can be fixed by myoblasts in vitro, and because it has the capacity to induce cell lys is, its possible role in the early death of transplanted myoblasts was investigated. CD1 mice and Macaca mulata monkeys were used as recipie nts for MT. In some mice, C3 was depleted before MT using Cobra Venom Factor. Mice were sacrificed during the first hour and up to 3 days af ter MT. Monkeys were biopsied 1 to 4 h after MT. Myoblast necrosis was assessed by the presence of intracellular calcium. Complement deposit ion was demonstrated by immunohistochemistry with anti-C3 and anti-C5b -9 neoantigen antibodies. In mice, C3 deposition was observed in damag ed muscle fibers and in regions containing necrosed myoblasts, Complem ent depletion did not diminish the proportion of necrosed cells. In mo nkeys, only a small percentage of transplanted myoblasts showed C3 or C5b-9 deposition, mostly intracellular, Complement activation seems no t to be implicated in directly damaging the transplanted cells, but se ems secondary to cellular death. Taking into account its chemotactic f unctions, complement could be implicated in the migration of neutrophi ls and macrophages into the clusters of transplanted cells. (C) 1998 E lsevier Science Inc.