Migration of adult myogenic precursor cells as revealed by GFP/nLacZ labelling of mouse transplantation chimeras

We studied the migratory behaviour of adult muscle precursor cells in the mouse into and from skeletal muscle grafts using green fluorescent protein (GFP) and nuclear LacZ transgenes as complementary and double markers of the cell's origin. Owing to the small molecular mass and extreme solubility of GFP, this label provided a drastically increased sensitivity for detection compared with the markers that had been used previously. During the first six weeks after the operation, the graft/host border was well defined, with only occasional local intermingling and co-fusion of host and donor myogenic cells. Seven to eleven weeks after the operation we found that the host myogenic cells had migrated into the graft, and graft myogenic cells had migrated into the adjacent host muscle, with integration of donor nuclei into pre-existing myotubes or muscle fibres. There was no indication of an origin of, or target for, these myogenic cells besides neighbouring muscles. Our observations indicate migration of these cells through solid muscle tissue, over a distance of several millimetres. The migratory activity of adult myogenic precursor cells can be stimulated by traumatic events in either the target muscle or the muscle of origin.

[1]  Daniel Eberhard,et al.  Localization of GFP in Frozen Sections from Unfixed Mouse Tissues: Immobilization of a Highly Soluble Marker Protein by Formaldehyde Vapor , 2003, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[2]  T. Partridge.  Stem cell route to neuromuscular therapies , 2003, Muscle & nerve.

[3]  N. Rosenthal,et al.  The Role of Stem Cells in Skeletal and Cardiac Muscle Repair , 2002, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[4]  M. Grounds,et al.  Absence of MyoD increases donor myoblast migration into host muscle. , 2001, Experimental cell research.

[5]  F. Mavilio,et al.  Bone-marrow transplantation: Failure to correct murine muscular dystrophy , 2001, Nature.

[6]  Giulio Cossu,et al.  Skeletal myogenic potential of human and mouse neural stem cells , 2000, Nature Neuroscience.

[7]  N. Caron,et al.  In vivo migration of transplanted myoblasts requires matrix metalloproteinase activity. , 2000, Experimental cell research.

[8]  M. Grounds,et al.  Why Do Cultured Transplanted Myoblasts Die in Vivo? DNA Quantification Shows Enhanced Survival of Donor Male Myoblasts in Host Mice Depleted of CD4+ and CD8+ Cells or NK1.1+ Cells , 2000, Cell transplantation.

[9]  M. Vacher,et al.  Translational diffusion of globular proteins in the cytoplasm of cultured muscle cells. , 2000, Biophysical journal.

[10]  N. Klopp,et al.  A MULTICOPY c‐myc TRANSGENE AS A NUCLEAR LABEL: OVERGROWTH OF Myctg50CELLS IN ALLOPHENIC MICE , 1998, Cell biology international.

[11]  G Cossu,et al.  Muscle regeneration by bone marrow-derived myogenic progenitors. , 1998, Science.

[12]  Tomoko Nakanishi,et al.  ‘Green mice’ as a source of ubiquitous green cells , 1997, FEBS letters.

[13]  R. Bischoff.  Chemotaxis of skeletal muscle satellite cells , 1997, Developmental dynamics : an official publication of the American Association of Anatomists.

[14]  C. Babinet,et al.  Cardiovascular lesions and skeletal myopathy in mice lacking desmin. , 1996, Developmental biology.

[15]  M. Grounds,et al.  A potential alternative strategy for myoblast transfer therapy: the use of sliced muscle grafts. , 1996, Cell transplantation.

[16]  G. Maréchal,et al.  Lack of myoblasts migration between transplanted and host muscles of mdx and normal mice , 1996, Journal of Muscle Research & Cell Motility.

[17]  M. England,et al.  Migration of muscle cells , 1994, Nature.

[18]  T. Partridge,et al.  Long-term persistence and migration of myogenic cells injected into pre-irradiated muscles of mdx mice , 1993, Journal of the Neurological Sciences.

[19]  M. Grounds,et al.  Transplantation in the mouse model--the use of a Y-chromosome-specific DNA clone to identify donor cells in situ. , 1991, Transplantation.

[20]  H. Jockusch,et al.  Inactivation of muscle chloride channel by transposon insertion in myotonic mice , 1991, Nature.

[21]  H. Blau,et al.  Migration of myoblasts across basal lamina during skeletal muscle development , 1990, Nature.

[22]  E. Füchtbauer,et al.  Developmental control of the excitability of muscle: transplantation experiments on a myotonic mouse mutant. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Carlson Bm.  Regeneration of entire skeletal muscles. , 1986 .

[24]  M. Grounds,et al.  Evidence of fusion between host and donor myoblasts in skeletal muscle grafts , 1978, Nature.

[25]  A. Bateman.  Mammalian Chimaeras , 1977, British Journal of Cancer.

[26]  M A Teillet,et al.  Experimental analysis of the migration and differentiation of neuroblasts of the autonomic nervous system and of neurectodermal mesenchymal derivatives, using a biological cell marking technique. , 1974, Developmental biology.

[27]  D. Watt,et al.  The movement of muscle precursor cells between adjacent regenerating muscles in the mouse , 2004, Anatomy and Embryology.

[28]  J. West.  Insights into development and genetics from mouse chimeras. , 1999, Current topics in developmental biology.

[29]  M. Grounds,et al.  Chemotaxis in myogenesis , 1996 .

[30]  B. Carlson.  Regeneration of entire skeletal muscles. , 1986, Federation proceedings.