Bone marrow-derived cell regulation of skeletal muscle regeneration.
Limb regeneration requires the coordination of multiple stem cell populations to recapitulate the process of tissue formation. Therefore, bone marrow (BM) -derived cell regulation of skeletal muscle regeneration was examined in mice lacking the CC chemokine receptor 2 (CCR2). Myofiber size, numbers of myogenic progenitor cells (MPCs), and recruitment of BM-derived cells and macrophages were assessed after cardiotoxin-induced injury of chimeric mice produced by transplanting BM from wild-type (WT) or CCR2(-/-) mice into irradiated WT or CCR2(-/-) host mice. Regardless of the host genotype, muscle regeneration and recruitment of BM-derived cells and macrophages were similar in mice replenished with WT BM, whereas BM-derived cells and macrophage accumulation were decreased and muscle regeneration was impaired in all animals receiving CCR2(-/-) BM. Furthermore, numbers of MPCs (CD34(+)/Sca-1(-)/CD45(-) cells) were significantly increased in mice receiving CCR2(-/-) BM despite the decreased size of regenerated myofibers. Thus, the expression of CCR2 on BM-derived cells regulated macrophage recruitment into injured muscle, numbers of MPC, and the extent of regenerated myofiber size, all of which were independent of CCR2 expression on host-derived cells. Future studies in regenerative medicine must include consideration of the role of BM-derived cells, possibly macrophages, in CCR2-dependent events that regulate effective skeletal muscle regeneration.
Sun
Dongxu
D
Department of Surgery, University of Texas Health Science Center, San Antonio, Texas, USA.
Martinez
Carlo O
CO
Ochoa
Oscar
O
Ruiz-Willhite
Lourdes
L
Bonilla
Jose R
JR
Centonze
Victoria E
VE
Waite
Lindsay L
LL
Michalek
Joel E
JE
McManus
Linda M
LM
Shireman
Paula K
PK
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D000950:Antigens, Ly / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016026:Bone Marrow Transplantation; D054715:Cardiotoxins / Q000633:toxicity; D002454:Cell Differentiation; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000166:cytology* / Q000293:injuries / Q000502:physiology* / Q000601:surgery; D054390:Receptors, CCR2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
D018952:Antigens, CD34; D000950:Antigens, Ly; D054715:Cardiotoxins; C515335:Ccr2 protein, mouse; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D054390:Receptors, CCR2; D017493:Leukocyte Common Antigens