Background: Duchenne muscular dystrophy (DMD) is an inherited progressive disorder that causes skeletal and cardiac muscle deterioration with chronic inflammation. Dental pulp stromal cells (DPSCs) are attractive candidates for cell-based strategies for DMD because of their immunosuppressive properties. Therefore, we hypothesized that systemic treatment with DPSCs might show therapeutic benefits as an anti-inflammatory therapy.
Methods: To investigate the potential benefits of DPSC transplantation for DMD, we examined the disease progression in DMD animal model, mdx mice, by comparing them with different systemic treatment conditions. The DPSC-treated model, a canine X-linked muscular dystrophy model in Japan (CXMDJ), which has a severe phenotype similar to that of DMD patients, also underwent comprehensive analysis, including histopathological findings, muscle function, and locomotor activity.
Results: We demonstrated a therapeutic strategy for the long-term functional recovery in DMD using repeated DPSC administration. DPSC-treated mdx mice and CXMDJ showed no serious adverse events. MRI findings and muscle histology suggested that DPSC treatment downregulated severe inflammation in DMD muscles and demonstrated a milder phenotype after DPSC treatment. DPSC-treated models showed an increased recovery in grip-hand strength and improved tetanic force and home-cage activity. Interestingly, maintenance of long-term running capability and stabilized cardiac function was also observed in 1-year-old DPSC-treated CXMDJ.
Conclusions: We developed a novel strategy for the safe and effective transplantation of DPSCs for DMD recovery, including repeated systemic injection to regulate inflammation at a young age. This is the first report on the efficacy 58 of systemic DPSC treatment, from which we can propose that DPSCs may play an important role in delaying the DMD disease phenotype.