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Background <p>The optimal timing for mesenchymal stem cell (MSC) therapy in Duchenne muscular dystrophy (DMD) remains unclear.</p> Methods <p>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.</p> Results <p>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 (<i>p</i> &lt; 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.</p> Conclusion <p>Early and sustained MSC administration offers superior structural and functional protection in DMD rats, highlighting the importance of treatment timing in maximizing therapeutic efficacy.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月26日

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  • Yuki Kihara,
  • Masanari Ikeda,
  • Ryo Takagi,
  • Keiko Ishigaki,
  • Keitaro Yamanouchi,
  • Satoru Nagata,
  • Masayuki Yamato

摘要

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.