Stem cell research & therapy · 2025
Continuous adipose-derived stem cell therapy from the neonatal stage effectively reduces Duchenne muscular dystrophy symptoms in rats.
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Kihara Yuki, Ikeda Masanari, Takagi Ryo, Ishigaki Keiko, Yamanouchi Keitaro, Nagata Satoru, Yamato Masayuki
Аннотация
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.
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.