Robust conversion of marrow cells to skeletal muscle with formation of marrow-derived muscle cell colonies: A multifactorial process

Mehrdad Abedi, Deborah A. Greer, Gerald A. Colvin, Delia A. Demers, Mark S. Dooner, Jasha A. Harpel, Heinz Ulrich Weier, Jean Francois Lambert, P. J. Quesenberry

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Objective Murine marrow cells are capable of repopulating skeletal muscle fibers. A point of concern has been the "robustness" of such conversions. We have investigated the impact of type of cell delivery, muscle injury, nature of delivered cell, and stem cell mobilizations on marrow-to-muscle conversion. Methods We transplanted green fluorescence protein (GFP)-transgenic marrow into irradiated C57BL/6 mice and then injured anterior tibialis muscle by cardiotoxin. One month after injury, sections were analyzed by standard and deconvolutional microscopy for expression of muscle and hematopoietic markers. Results Irradiation was essential to conversion, although whether by injury or induction of chimerism is not clear. Cardiotoxin- and, to a lesser extent, PBS-injected muscles showed significant number of GFP + muscle fibers, while uninjected muscles showed only rare GFP + cells. Marrow conversion to muscle was increased by two cycles of G-CSF mobilization and to a lesser extent by G-CSF and steel or GM-CSF. Transplantation of female GFP to male C57BL/6 and GFP to ROSA26 mice showed fusion of donor cells to recipient muscle. High numbers of donor-derived muscle colonies and up to 12% GFP+ muscle cells were seen after mobilization or direct injection. These levels of donor muscle chimerism approach levels that could be clinically significant in developing strategies for the treatment of muscular dystrophies. Conclusion In summary, the conversion of marrow to skeletal muscle cells is based on cell fusion and is critically dependent on injury. This conversion is also numerically significant and increases with mobilization.

Original languageEnglish (US)
Pages (from-to)426-434
Number of pages9
JournalExperimental Hematology
Volume32
Issue number5
DOIs
StatePublished - May 2004
Externally publishedYes

Fingerprint

Muscle Cells
Skeletal Muscle
Bone Marrow
Muscles
Fluorescence
Cardiotoxins
Chimerism
Cell Fusion
Wounds and Injuries
Granulocyte Colony-Stimulating Factor
Proteins
Hematopoietic Stem Cell Mobilization
Muscle Proteins
Muscular Dystrophies
Steel
Skeletal Muscle Fibers
Granulocyte-Macrophage Colony-Stimulating Factor
Inbred C57BL Mouse
Microscopy
Transplantation

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Robust conversion of marrow cells to skeletal muscle with formation of marrow-derived muscle cell colonies : A multifactorial process. / Abedi, Mehrdad; Greer, Deborah A.; Colvin, Gerald A.; Demers, Delia A.; Dooner, Mark S.; Harpel, Jasha A.; Weier, Heinz Ulrich; Lambert, Jean Francois; Quesenberry, P. J.

In: Experimental Hematology, Vol. 32, No. 5, 05.2004, p. 426-434.

Research output: Contribution to journalArticle

Abedi, M, Greer, DA, Colvin, GA, Demers, DA, Dooner, MS, Harpel, JA, Weier, HU, Lambert, JF & Quesenberry, PJ 2004, 'Robust conversion of marrow cells to skeletal muscle with formation of marrow-derived muscle cell colonies: A multifactorial process', Experimental Hematology, vol. 32, no. 5, pp. 426-434. https://doi.org/10.1016/j.exphem.2004.02.007
Abedi, Mehrdad ; Greer, Deborah A. ; Colvin, Gerald A. ; Demers, Delia A. ; Dooner, Mark S. ; Harpel, Jasha A. ; Weier, Heinz Ulrich ; Lambert, Jean Francois ; Quesenberry, P. J. / Robust conversion of marrow cells to skeletal muscle with formation of marrow-derived muscle cell colonies : A multifactorial process. In: Experimental Hematology. 2004 ; Vol. 32, No. 5. pp. 426-434.
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AU - Demers, Delia A.

AU - Dooner, Mark S.

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AU - Weier, Heinz Ulrich

AU - Lambert, Jean Francois

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N2 - Objective Murine marrow cells are capable of repopulating skeletal muscle fibers. A point of concern has been the "robustness" of such conversions. We have investigated the impact of type of cell delivery, muscle injury, nature of delivered cell, and stem cell mobilizations on marrow-to-muscle conversion. Methods We transplanted green fluorescence protein (GFP)-transgenic marrow into irradiated C57BL/6 mice and then injured anterior tibialis muscle by cardiotoxin. One month after injury, sections were analyzed by standard and deconvolutional microscopy for expression of muscle and hematopoietic markers. Results Irradiation was essential to conversion, although whether by injury or induction of chimerism is not clear. Cardiotoxin- and, to a lesser extent, PBS-injected muscles showed significant number of GFP + muscle fibers, while uninjected muscles showed only rare GFP + cells. Marrow conversion to muscle was increased by two cycles of G-CSF mobilization and to a lesser extent by G-CSF and steel or GM-CSF. Transplantation of female GFP to male C57BL/6 and GFP to ROSA26 mice showed fusion of donor cells to recipient muscle. High numbers of donor-derived muscle colonies and up to 12% GFP+ muscle cells were seen after mobilization or direct injection. These levels of donor muscle chimerism approach levels that could be clinically significant in developing strategies for the treatment of muscular dystrophies. Conclusion In summary, the conversion of marrow to skeletal muscle cells is based on cell fusion and is critically dependent on injury. This conversion is also numerically significant and increases with mobilization.

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