Blood borne macrophages are essential for the triggering of muscle regeneration following muscle transplant

The transplantation of satellite cells may constitute a strategy for rebuil ding muscle fibres in inherited myopathies. However, its development requir es a great understanding of the role of environmental signals in the regene rative process. It is therefore essential to identify the key events trigge ring and controlling this process in vivo. We investigated whether macropha ges play a key role in the course of the regenerative process using skeleta l muscle transplants from transgenic pHuDes-nls-LacZ mice. Before grafting, transplants were conditioned with macrophage inflammatory protein 1-beta ( MIP 1-beta; stimulating the macrophages infiltration or vascular endothelia l growth factor (VEGF) stimulating angiogenesis). Treatment of transplants with MIP 1-beta and VEGF both accelerated and augmented monocyte-macrophage infiltration and satellite cell differentiation and/or proliferation, as c ompared to controls. In addition, VEGF treatment enhanced the number of new ly formed myotubes. When a complete depletion of host monocyte-macrophages was experimentally induced, no regeneration occurred in transplants. Our da ta suggest that the presence of blood borne macrophages is required for tri ggering the earliest events of skeletal muscle regeneration. The understand ing of macrophage behaviour after muscle injury should allow us to develop future strategies of satellite cell, transplantation as a treatment for mus cular dystrophies. (C) 1999 Elsevier Science B.V. All rights reserved.