238. Cell Therapeutic Approach Using Dental Pulp Stromal Cells for Duchenne Muscular Dystrophy

Abstract

Background: Duchenne muscular dystrophy (DMD) is an incurable genetic disease with early mortality that exhibits skeletal muscle weakness with chronic inflammation. Dental pulp stromal cells (DPCs) could be potential therapeutics because of their immunosuppressive properties and multipotency. In the present study, we examined the strategies for effective cell transplantation to develop a novel approach for functional recovery of the skeletal as well as cardiac muscles using a dog model of Duchenne muscular dystrophy. Methods: DPCs were intravenously injected into two littermates of canine X-linked muscular dystrophy in Japan (CXMDJ) at weekly interval for 8 weeks without immunosuppression. Clinical phenotypes in the transplanted dogs were analyzed by using blood exams, physical capacity, magnetic resonance imaging (MRI) analysis compared with non-injected littermates as controls. Results: The downregulation of inflammation in the lower legs of DPCs-treated CXMDJ was confirmed by MRI analysis. Serum levels of pro-inflammatory cytokine IL-6 were well regulated in the treated CXMDJ during experiments, unlike non-injected dogs. Although CXMDJ showed progressive muscle atrophy in the all four limbs, exercise intolerance and abnormal locomotion, we observed improved phenotypes in the DPCs-treated CXMDJ along with the improved pace of walking and running. Conclusion: We suggested that the systemic injection of DPCs ameliorated the progressive phenotype in CXMDJ. The therapeutic effects might be associated with the production of paracrine or endocrine factors that regulate inflammation, and might also stimulate the proliferation of endogenous stem cells at the injured muscle tissue. This strategy of DPCs treatment would be promising for the future DMD cell therapy.