Mac-1(low) early myeloid cells in the bone marrow-derived SP fraction migrate into injured skeletal muscle and participate in muscle regeneration.
Recent studies have shown that bone marrow (BM) cells, including the BM side population (BM-SP) cells that enrich hematopoietic stem cells (HSCs), are incorporated into skeletal muscle during regeneration, but it is not clear how and what kinds of BM cells contribute to muscle fiber regeneration. We found that a large number of SP cells migrated from BM to muscles following injury in BM-transplanted mice. These BM-derived SP cells in regenerating muscles expressed different surface markers from those of HSCs and could not reconstitute the mouse blood system. BM-derived SP/Mac-1(low) cells increased in number in regenerating muscles following injury. Importantly, our co-culture studies with activated satellite cells revealed that this fraction carried significant potential for myogenic differentiation. By contrast, mature inflammatory (Mac-1(high)) cells showed negligible myogenic activities. Further, these BM-derived SP/Mac-1(low) cells gave rise to mononucleate myocytes, indicating that their myogenesis was not caused by stochastic fusion with host myogenic cells, although they required cell-to-cell contact with myogenic cells for muscle differentiation. Taken together, our data suggest that neither HSCs nor mature inflammatory cells, but Mac-1(low) early myeloid cells in the BM-derived SP fraction, play an important role in regenerating skeletal muscles.
Ojima
Koichi
K
Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.
Uezumi
Akiyoshi
A
Miyoshi
Hiroyuki
H
Masuda
Satoru
S
Morita
Yohei
Y
Fukase
Akiko
A
Hattori
Akihito
A
Nakauchi
Hiromitsu
H
Miyagoe-Suzuki
Yuko
Y
Takeda
Shin'ichi
S
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology; D002454:Cell Differentiation; D002465:Cell Movement; D049452:Green Fluorescent Proteins; D006410:Hematopoiesis; D008164:Luminescent Proteins / Q000235:genetics; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000293:injuries / Q000502:physiology*; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology* / Q000502:physiology*; D012038:Regeneration
D008164:Luminescent Proteins; D016177:Macrophage-1 Antigen; D049452:Green Fluorescent Proteins