Muscular Dystrophy Stem Cell Treatment

Muscular Dystrophy and Stem Cell Therapy

What is Muscular Dystrophy?

Muscular Dystrophy and Stem Cell Therapy

Muscular Dystrophy and Stem Cell Therapy

Muscular Dystrophy (MD) refers to a group of hereditary muscle diseases that weakens the muscles that move the human body.
Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.

Nine diseases including Duchenne, Becker, limb girdle, congenital, facioscapulohumeral, myotonic, oculopharyngeal, distal, and Emery-Dreifuss are always classified as muscular dystrophy but there are more than 100 diseases in total with similarities to muscular dystrophy.

Most types of MD are multi-system disorders with manifestations in body systems including the heart, gastrointestinal and nervous systems, endocrine glands, skin, eyes and even brain.

The condition may also lead to mood swings and learning difficulties.


Effective myotube formation in human adipose tissue-derived stem cells expressing dystrophin and myosin heavy chain by cellular fusion with mouse C2C12 myoblasts.

Biochem Biophys Res Commun. 2011 Apr 5;

Authors: Eom YW, Lee JE, Yang MS, Jang IK, Kim HE, Lee DH, Kim YJ, Park WJ, Kong JH, Shim KY, Lee JI, Kim HS

Stem cell therapy for muscular dystrophies requires stem cells that are able to participate in the formation of new muscle fibers. However, the differentiation steps that are the most critical for this process are not clear.

We investigated the myogenic phases of human adipose tissue-derived stem cells (hASCs) step by step and the capability of myotube formation according to the differentiation phase by cellular fusion with mouse myoblast C2C12 cells.

In hASCs treated with 5-azacytidine and fibroblast growth factor-2 (FGF-2) for 1day, the early differentiation step to express MyoD and myogenin was induced by FGF-2 treatment for 6days. Dystrophin and myosin heavy chain (MyHC) expression was induced by hASC conditioned medium in the late differentiation step.

Myotubes were observed only in hASCs undergoing the late differentiation step by cellular fusion with C2C12 cells. In contrast, hASCs that were normal or in the early stage were not involved in myotube formation.

Our results indicate that stem cells expressing dystrophin and MyHC are more suitable for myotube formation by co-culture with myoblasts than normal or early differentiated stem cells expressing MyoD and myogenin.

PMID: 21473854 [PubMed - as supplied by publisher]

Related Articles Confirmation of donor-derived dystrophin in a duchenne muscular dystrophy patient allotransplanted with normal myoblasts. Muscle Nerve. 2016 11;54(5):979-981 Authors: Skuk D, Tremblay JP PMID: 27060858 [PubMed - indexed for MEDLINE]
Related Articles Recapitulating muscle disease phenotypes with myotonic dystrophy 1 iPS cells: a tool for disease modeling and drug discovery. Dis Model Mech. 2018 Jun 13;: Authors: Mondragon-Gonzalez R, Perlingeiro RCR Abstract Myotonic Dystrophy 1 (DM1) is a multi-system disorder primarily affecting the central nervous system, heart and skeletal muscle. It is caused by an expansion of the CTG trinucleotide repeats in the 3' untranslated region of the DMPK gene. Although patient myoblasts have been used for studying the disease in vitro, the invasiveness as well as the low accessibility to muscle biopsies motivate the development of alternative reliable myogenic models. Here, we established two DM1 iPS cell lines from patient-derived fibroblasts, and using the PAX7 conditional expression system, differentiated these into myogenic progenitors, and subsequently, terminally differentiated myotubes. Both DM1 myogenic progenitors and myotubes were found to express the intranuclear RNA foci exhibiting sequestration of MBNL1. Moreover, we found the DM1-related mis-splicing, namely BIN1 exon 11 in DM1 myotubes. We use this model to test a specific therapy, antisense oligonucleotide treatment, and find that this efficiently abolished RNA foci and rescued BIN1 mis-splicing in DM1 iPS cell-derived myotubes. Together, our results demonstrate that myotubes derived from DM1 iPS cells recapitulate the critical molecular features of DM1 and are sensitive to ASO treatment, confirming that these cells can be used for in vitro disease modeling and candidate drug testing or screening. PMID: 29898953 [PubMed - as supplied by publisher]

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