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Transplantation. 2009 May 15;87(9):1275-82. doi: 10.1097/TP.0b013e3181a1719b.

Muscular dystrophy therapy by nonautologous mesenchymal stem cells: muscle regeneration without immunosuppression and inflammation.

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  • 1Department of Biochemistry, University at Buffalo, Buffalo, NY 14214, USA.

Abstract

BACKGROUND:

The use of nonautologous stem cells isolated from healthy donors for stem-cell therapy is an attractive approach, because the stem cells can be culture expanded in advance, thoroughly tested, and formulated into off-the-shelf medicine. However, human leukocyte antigen compatibility and related immunosuppressive protocols can compromise therapeutic efficacy and cause unwanted side effects.

METHODS:

Mesenchymal stem cells (MSCs) have been postulated to possess unique immune regulatory function. We explored the immunomodulatory property of human and porcine MSCs for the treatment of delta-sarcoglycan-deficient dystrophic hamster muscle without immunosuppression. Circulating and tissue markers of inflammation were analyzed. Muscle regeneration and stem-cell fate were characterized.

RESULTS:

Total white blood cell counts and leukocyte-distribution profiles were similar among the saline- and MSC-injected dystrophic hamsters 1 month posttreatment. Circulating levels of immunoglobulin A, vascular cell adhesion molecule-1, myeloperoxidase, and major cytokines involved in inflammatory response were not elevated by MSCs, nor were expression of the leukocyte common antigen CD45 and the cytokine transcriptional activator NF-kappaB in the injected muscle. Treated muscles exhibited increased cell-cycle activity and attenuated oxidative stress. Injected MSCs were found to be trapped in the musculature, contribute to both preexisting and new muscle fibers, and mediates capillary formation.

CONCLUSIONS:

Intramuscular injection of nonautologous MSCs can be safely used for the treatment of dystrophic muscle in immunocompetent hosts without inflaming the host immune system.

PMID:
19424025
PMCID:
PMC2746453
DOI:
10.1097/TP.0b013e3181a1719b
[PubMed - indexed for MEDLINE]
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