Long-term Engraftment of Multipotent Mesenchymal Stromal Cells That Differentiate to Form Myogenic Cells in Dogs With Duchenne Muscular Dystrophy
| Autor: | Hironori Okada, Shin'ichi Takeda, Michiko Wada-Maeda, Sachiko Ohshima-Hosoyama, Yuko Nitahara-Kasahara, Takashi Okada, Akinori Nakamura, Hiromi Hayashita-Kinoh |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Cellular differentiation Duchenne muscular dystrophy Bone Marrow Cells Cell Separation Biology Naphthalenes MyoD Mesenchymal Stem Cell Transplantation Muscle Development Injections Intramuscular Immunophenotyping MyoD Protein Dogs Drug Discovery medicine Genetics Animals Humans Cell Lineage Muscular dystrophy Adapalene Molecular Biology Immunosuppression Therapy Pharmacology Myogenesis Multipotent Stem Cells Mesenchymal stem cell Graft Survival Cell Differentiation Mesenchymal Stem Cells medicine.disease Muscular Dystrophy Duchenne HEK293 Cells Injections Intra-Arterial Multipotent Stem Cell Immunology Cancer research Molecular Medicine Female Original Article |
| Zdroj: | Molecular Therapy. 20(1):168-177 |
| ISSN: | 1525-0016 |
| DOI: | 10.1038/mt.2011.181 |
| Popis: | Duchenne muscular dystrophy (DMD) is an incurable genetic disease with early mortality. Multipotent mesenchymal stromal cells (MSCs) are of interest because of their ability to differentiate to form myogenic cells in situ. In the present study, methods were developed to expand cultures of MSCs and to promote the myogenic differentiation of these cells, which were then used in a new approach for the treatment of DMD. MSC cultures enriched in CD271(+) cells grew better than CD271-depleted cultures. The transduction of CD271(+) MSCs with MyoD caused myogenic differentiation in vitro and the formation of myotubes expressing late myogenic markers. CD271(+) MSCs in the myogenic cell lineage transplanted into dog leukocyte antigen (DLA)-identical dogs formed clusters of muscle-like tissue. Intra-arterial injection of the CD271(+) MSCs resulted in engraftment at the site of the cardiotoxin (CTX)-injured muscle. Dogs affected by X-linked muscular dystrophy in Japan (CXMD(J)) treated with an intramuscular injection of CD271(+) MSCs similarly developed muscle-like tissue within 8-12 weeks in the absence of immunosuppression. In the newly formed tissues, developmental myosin heavy chain (dMyHC) and dystrophin were upregulated. These findings demonstrate that a cell transplantation strategy using CD271(+) MSCs may offer a promising treatment approach for patients with DMD. |
| Databáze: | OpenAIRE |
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