Bone marrow side population cells are enriched for progenitors capable of myogenic differentiation.
Although the contribution of bone marrow-derived cells to regenerating skeletal muscle has been repeatedly documented, there remains considerable debate as to whether this incorporation is exclusively a result of inflammatory cell fusion to regenerating myofibers or whether certain populations of bone marrow-derived cells have the capacity to differentiate into muscle. The present study uses a dual-marker approach in which GFP(+) cells were intravenously transplanted into lethally irradiated beta-galactosidase(+) recipients to allow for simple determination of donor and host contribution to the muscle. FACS analysis of cardiotoxin-damaged muscle revealed that CD45(+) bone-marrow side-population (SP) cells, a group enriched in hematopoietic stem cells, can give rise to CD45(-)/Sca-1(+)/desmin(+) cells capable of myogenic differentiation. Moreover, after immunohistochemical examination of the muscles of both SP- and whole bone marrow-transplanted animals, we noted the presence of myofibers composed only of bone marrow-derived cells. Our findings suggest that a subpopulation of bone marrow SP cells contains precursor cells whose progeny have the potential to differentiate towards a muscle lineage and are capable of de novo myogenesis following transplantation and initiation of muscle repair via chemical damage.
Luth
Eric S
ES
Program in Genomics, Division of Genetics, Children's Hospital Boston, Boston, MA 02115, USA.
Jun
Susan J
SJ
Wessen
McKenzie K
MK
Liadaki
Kalliopi
K
Gussoni
Emanuela
E
Kunkel
Louis M
LM
D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D002452:Cell Count; D002454:Cell Differentiation; D019070:Cell Lineage; D002469:Cell Separation; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology*; D001616:beta-Galactosidase / Q000378:metabolism
D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D015415:Biomarkers; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D049452:Green Fluorescent Proteins; D017493:Leukocyte Common Antigens; D001616:beta-Galactosidase