Abstract
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 α-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.
| Original language | English |
|---|---|
| Pages (from-to) | 74-85 |
| Number of pages | 12 |
| Journal | Experimental Cell Research |
| Volume | 277 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2002 |
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Keywords
- Bone marrow
- Cell transplantation
- Dystrophin
- Gene therapy
- Stem cell
ASJC Scopus subject areas
- Cell Biology
Cite this
A subpopulation of murine bone marrow cells fully differentiates along the myogenic pathway and participates in muscle repair in the mdx dystrophic mouse. / Corti, S.; Strazzer, S.; Del Bo, R.; Salani, S.; Bossolasco, P.; Fortunato, F.; Locatelli, F.; Soligo, D.; Moggio, M.; Ciscato, P.; Prelle, A.; Borsotti, C.; Bresolin, N.; Scarlato, G.; Comi, G. P.
In: Experimental Cell Research, Vol. 277, No. 1, 2002, p. 74-85.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A subpopulation of murine bone marrow cells fully differentiates along the myogenic pathway and participates in muscle repair in the mdx dystrophic mouse
AU - Corti, S.
AU - Strazzer, S.
AU - Del Bo, R.
AU - Salani, S.
AU - Bossolasco, P.
AU - Fortunato, F.
AU - Locatelli, F.
AU - Soligo, D.
AU - Moggio, M.
AU - Ciscato, P.
AU - Prelle, A.
AU - Borsotti, C.
AU - Bresolin, N.
AU - Scarlato, G.
AU - Comi, G. P.
PY - 2002
Y1 - 2002
N2 - 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 α-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.
AB - 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 α-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.
KW - Bone marrow
KW - Cell transplantation
KW - Dystrophin
KW - Gene therapy
KW - Stem cell
UR - http://www.scopus.com/inward/record.url?scp=0036343850&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036343850&partnerID=8YFLogxK
U2 - 10.1006/excr.2002.5543
DO - 10.1006/excr.2002.5543
M3 - Article
C2 - 12061818
AN - SCOPUS:0036343850
VL - 277
SP - 74
EP - 85
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 1
ER -