Background: Transplant of Chimeric Cells, created via ex vivo fusion of donor and recipient cells, represents a promising cell therapy option in the field of tissue regeneration, as eliminates the need of life-long immunosuppression. Duchenne Muscular Dystrophy, the most common type of muscular dystrophies, is a progressive and lethal disease, caused by X-linked genetic mutations and is affecting the production and function of dystrophin in the muscle cells. Allogeneic stem cell transplant therapies are aiming to restore dystrophin in affected muscles, however, are challenged by rejection and limited engraftment.

The aim of this study was to test the feasibility of a novel Duchenne Muscular Dystrophy Chimeric Cells (DMDCC) therapy of mesenchymal stem cells (MSC) and myoblasts origin through in vitro characterization of phenotype, genotype and proliferative potential of DMDCC and through in vivo assessment of the survival and engraftment of DMDCC in DMD scid/mdx mice models.

Methods: Twelve ex vivo fusions of allogenic human myoblasts and MSC were performed, using polyethylene glycol technique. DMDCC phenotype and genotype were evaluated by flow cytometry, confocal microscopy and PCR. DMDCC were cultured up to 30 days to test proliferation capacity. In Group 1, scid/mdx mice received 0.5×10⁶ human DMDCC of myoblast/MSC origin through multiple intramuscular injections. Control animals received 60[mu]l of PBS in group 2, and human MSC and myoblast without fusion (0.25×10⁶ each) in group 3. Therapeutic effect of DMDCC was assessed by measurements of muscle weight, inflammation, atrophy, muscle fibrosis, dystrophin expression and muscle function (grip strength test) at day 7 after transplant.

Results: After successful fusion procedure, DMDCC expressed antigens of both parent cells and maintained proliferative capacity in long-term cultures. DMDCC treated mdx/scid recipients showed DMDCC engraftment in gastrocnemius muscle and locally increased dystrophin expression (12%), as early as 7 day post-transplant. Control animals treated with MSC and myoblasts without fusion showed no engraftment and migration to perivascular areas.

Conclusion: This study confirmed feasibility of myoblast and MSC fusion and the created DMDCC showed successful engraftment and restoration of dystrophin in affected muscles. Upon long-term follow-up results, DMDCC therapy may represent a novel, universal approach for treatment of various muscular dystrophies.

CITATION INFORMATION: Szilagyi E, Bryndza Tfaily E, Cwykiel J, Siemionow M. Chimeric Cell Transplantation for Treatment of Duchenne Muscular Dystrophy: A Preliminary Report. Am J Transplant. 2016;16 (suppl 3).

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