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<p>Cerebral palsy (CP), the most prevalent pediatric motor disorder with significant cognitive comorbidity (&gt; 50%), lacks therapies addressing both impairments in moderate-to-severe cases. This study demonstrates that human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) exert profound therapeutic effects in a rat model of moderate-to-severe CP established via bilateral carotid artery occlusion with hypoxia. Intravenously administered hUCMSC-Exos displayed sustained brain retention and significantly restored motor coordination and cognitive function. The recovery was primarily mediated through enhanced remyelination driven by promoted oligodendrocyte maturation and differentiation (elevated oligodendrocyte lineage transcription factor 2 and myelin basic protein). Concurrently, the treatment attenuated key pathological processes involving sustained neuroinflammatory responses (reduced ionized calcium-binding adapter molecule 1, tumor necrosis factor-α, and interleukin-6) while elevating brain-derived neurotrophic factor. Our findings establish hUCMSC-Exos as a promising dual-modality therapy for moderate-to-severe CP, mechanistically linked to robust remyelination and coordinated modulation of core disease mechanisms.</p> Graphical Abstract <p></p>

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Stem Cell-Derived Exosomes Improve Neurological Dysfunction in a Rat Model of Moderate-to-Severe Cerebral Palsy

  • 期刊论文

  • 发表日期：

    2026年2月23日

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  • Tingting Peng Jr,
  • Huijuan Lin,
  • Xiaoli Zeng,
  • Yunlan Xie,
  • Jie Luo,
  • Lingjie Zhang,
  • Shiya Huang,
  • Zhiyi Ye,
  • Xiaolin Guo,
  • Wen Le,
  • Mingtong Zhang,
  • Wenhui Li,
  • Tingting Peng Sr,
  • Liru Liu,
  • Mingshan Han,
  • Ting Gao,
  • Hongmei Tang,
  • Jing Zhang,
  • Lu He,
  • Kaishou Xu

摘要

Cerebral palsy (CP), the most prevalent pediatric motor disorder with significant cognitive comorbidity (> 50%), lacks therapies addressing both impairments in moderate-to-severe cases. This study demonstrates that human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) exert profound therapeutic effects in a rat model of moderate-to-severe CP established via bilateral carotid artery occlusion with hypoxia. Intravenously administered hUCMSC-Exos displayed sustained brain retention and significantly restored motor coordination and cognitive function. The recovery was primarily mediated through enhanced remyelination driven by promoted oligodendrocyte maturation and differentiation (elevated oligodendrocyte lineage transcription factor 2 and myelin basic protein). Concurrently, the treatment attenuated key pathological processes involving sustained neuroinflammatory responses (reduced ionized calcium-binding adapter molecule 1, tumor necrosis factor-α, and interleukin-6) while elevating brain-derived neurotrophic factor. Our findings establish hUCMSC-Exos as a promising dual-modality therapy for moderate-to-severe CP, mechanistically linked to robust remyelination and coordinated modulation of core disease mechanisms.

Graphical Abstract