A subpopulation of murine bone marrow cells fully differentiates along the myogenic pathway and participates in muscle repair in the mdx dystrophic mouse.
Bone marrow (BM) transplantation in mice suggests the existence of pluripotent cells able to differentiate into skeletal muscle tissue, although sustained myofiber reconstitution has not yet been achieved. We investigated the myogenic potential of mouse BM cells and evaluated whether a BM fraction enriched for cells expressing skeletal muscle markers would ameliorate muscle repair, when compared to whole BM, into the dystrophic mdx mouse. We demonstrate that cells expressing striated-muscle-specific proteins are already present in the BM independently from experimentally forced myogenic conversion. We observed the presence of both markers of early myogenic program such as Pax3, Myf5, MyoD, desmin, and late myogenesis such as myosin heavy chain and alpha-sarcomeric actin. These myogenic cells are more represented in the early nonadherent BM fraction, which generates clones able to fully differentiate into myotubes. Transplantation in mdx mice by intravenous injection of whole BM and a tenfold BM myogenic enriched fraction resulted in BM reconstitution and limited dystrophin restoration. Taken together, these data show that a fraction of BM cells have a definite potential for differentiation along the skeletal muscle pathway and can be recruited by muscle repair mechanisms. They also indicate that factors limiting the degree of muscle recruitment and the host stem cell competition should be assessed in order to evaluate the usefulness of BM-derived myogenic cells into the context of cell-mediated gene therapy of inherited muscle diseases.
Corti
S
S
Dipartimento di Scienze Neurologiche, Centro Dino Ferrari, Università di Milano, I.R.C.C.S. Ospedale Maggiore Policlinico, Italy. stcorti@yahoo.it
Strazzer
S
S
Del Bo
R
R
Salani
S
S
Bossolasco
P
P
Fortunato
F
F
Locatelli
F
F
Soligo
D
D
Moggio
M
M
Ciscato
P
P
Prelle
A
A
Borsotti
C
C
Bresolin
N
N
Scarlato
G
G
Comi
G P
GP
D000818:Animals; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D002458:Cell Fractionation; D002469:Cell Separation; D002478:Cells, Cultured; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000235:genetics; D003893:Desmin / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D018380:Hematopoietic Stem Cell Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009124:Muscle Proteins / Q000235:genetics; D009132:Muscles / Q000166:cytology* / Q000378:metabolism; D009136:Muscular Dystrophies; D017570:MyoD Protein / Q000235:genetics; D051787:Myogenic Regulatory Factor 5; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors
D015415:Biomarkers; D004268:DNA-Binding Proteins; D003893:Desmin; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; C068686:Pax3 protein, mouse