Experimental Cell Research
Vol. 277, No. 1, July 1, 2002
ISSN: 0014-4827
EISSN: 1090-2422
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A Subpopulation of Murine Bone Marrow Cells Fully Differentiates along the Myogenic Pathway and Participates in Muscle Repair in the mdx Dystrophic Mouse
pp. 74-85 (doi:10.1006/excr.2002.5543) 
S. Corti*12 S. Strazzer*, 1 R. Del Bo* S. Salani P. Bossolasco, § F. Fortunato* F. Locatelli* D. Soligo, § M. Moggio* P. Ciscato* A. Prelle* C. Borsotti§ N. Bresolin*,  G. Scarlato* G. P. Comi*  

*Dipartimento di Scienze Neurologiche, Centro Dino Ferrari, Università di Milano, I.R.C.C.S. Ospedale Maggiore Policlinico, Milan, Italy
I.R.C.C.S. Eugenio Medea, Bosisio Parini, Lecco, Italy
Centro Trapianti di Midollo, I.R.C.C.S. Ospedale Maggiore Policlinico, Milan, Italy
§Fondazione Matarelli, Milan, Italy
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  • Corti, S [IDEAL] 
  • Strazzer, S [IDEAL] 
  • Del Bo, R [IDEAL] 
  • Salani, S [IDEAL] 
  • Bossolasco, P [IDEAL] 
  • Fortunato, F [IDEAL] 
  • Locatelli, F [IDEAL] 
  • Soligo, D [IDEAL] 
  • Moggio, M [IDEAL] 
  • Ciscato, P [IDEAL] 
  • Prelle, A [IDEAL] 
  • Borsotti, C [IDEAL] 
  • Bresolin, N [IDEAL] 
  • Scarlato, G [IDEAL] 
  • Comi, GP [IDEAL] 
  • (Received November 19, 2001; received in revised form February 25, 2002; published electronically June 12, 2002)
    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 -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. © 2002 Elsevier Science (USA).


    Key Words:  stem cell; gene therapy; bone marrow; dystrophin; cell transplantation

    1These authors contributed equally to this work.

    2To whom correspondence and reprint requests should be addressed at Dipartimento di Scienze Neurologiche, Universit à di Milano, Padiglione Ponti, Ospedale Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy. Fax: 39-02-55190392. E-mail: [email protected] .

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