Continuous adipose-derived stem cell therapy from the neonatal stage effectively reduces Duchenne muscular dystrophy symptoms in rats

Abstract

Background: The optimal timing for mesenchymal stem cell (MSC) therapy in Duchenne muscular dystrophy (DMD) remains unclear. Methods: Neonatal DMD rats received intraperitoneal adipose-derived MSCs according to three schedules: early (postnatal days 1 and 14), continuous (days 1, 14, 28, and 42), or late (days 28 and 42). Wild-type rats and untreated DMD rats served as controls. Functional and histological outcomes were assessed on day 56. Results: Continuous administration significantly attenuated the decline in grip strength across ten consecutive measurements (− 11% vs. −37% in DMD controls), and also reduced serum creatine kinase levels and diaphragmatic fibrosis (p < 0.05). Early or late treatment alone showed limited benefit. GFP-labelled cells were rarely detected in muscle, indicating minimal engraftment and suggesting paracrine-mediated effects. Molecular profiling showed lower CDKN2A together with higher CDKN1A, IL-10, VEGF-A and IGF-1 in the continuous group, revealing an anti-senescence, pro-regenerative profile that paralleled the functional gains. Conclusion: Early and sustained MSC administration offers superior structural and functional protection in DMD rats, highlighting the importance of treatment timing in maximizing therapeutic efficacy.