Repeated Intrathecal Stem Cells Optimize Neuroplasticity and Motor Function in Moderate-to-Severe Cerebral Palsy of...

Area of Science:

• Neuroscience
• Regenerative Medicine
• Stem Cell Biology

Background:

• Cerebral palsy (CP) is a debilitating neurological disorder with limited treatment options.
• Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) show promise for CP treatment, but optimal administration frequency is unknown.
• Existing CP models often represent mild injury, unlike the moderate-to-severe cases requiring more effective therapies.

Purpose of the Study:

• To investigate the efficacy and mechanism of hUC-MSCs in a rat model of moderate-to-severe CP (bilateral carotid artery occlusion [BCAO]).
• To compare the therapeutic effects of single versus repeated hUC-MSC intrathecal injections.
• To elucidate the underlying mechanisms of hUC-MSC treatment in CP.

Main Methods:

• Established a moderate-to-severe CP rat model using bilateral carotid artery occlusion (BCAO) on postnatal Day 4.
• Administered single or repeated intrathecal injections of hUC-MSCs on specific postnatal days.
• Assessed motor performance using rotarod and front-limb suspension tests.
• Evaluated neuronal regeneration, inflammation, and myelin integrity via biomarker analysis (NeuN, Iba-1, GFAP, MBP, BDNF).

Main Results:

• The BCAO model demonstrated more severe brain damage and motor deficits than the unilateral carotid artery occlusion (UCAO) model.
• hUC-MSCs successfully integrated into damaged brain areas and survived for at least 3 days post-injection.
• Both single and repeated hUC-MSC injections improved behavioral and histological outcomes.
• Repeated injections yielded significantly greater therapeutic benefits than single injections, including improved myelin structure, reduced inflammation, and enhanced neurotrophic support.

Conclusions:

• Repeated intrathecal administration of hUC-MSCs is a superior therapeutic strategy for moderate-to-severe CP compared to single injections.
• hUC-MSC treatment promotes neuronal recovery by improving myelin, reducing neuroinflammation, and increasing neurotrophic factors.
• This study provides a foundation for developing optimized hUC-MSC-based therapies for CP.