Therapeutic effect of amniotic membrane mesenchymal stem cell-derived exosome-rich conditioned medium in cerebral palsy model.

Abstract

BACKGROUND: Cerebral palsy (CP), primarily caused by perinatal cerebral hypoxia and ischemia, is a devastating neurological disease in children characterized by motor, behavioral, and cognitive disorders. This study aimed to evaluate the therapeutic effects of amniotic membrane mesenchymal stem cell-derived exosome-rich conditioned medium (ERCM) in a CP model. METHODS: ERCM components were analyzed using enzyme-linked immunosorbent assay. Biodistribution was examined via fluorescence-labeled ERCM in both normal and CP induced animals. In vitro, the neuroprotective effects of ERCM against lipopolysaccharide and potassium cyanide-induced cytotoxicity were assessed in human neural stem cells and oligodendrocyte progenitor cells, focusing on apoptosis, inflammation, and oligodendrocyte differentiation. In vivo, ERCM was injected into CP-induced animals, followed by evaluation of antiapoptotic and anti-inflammatory signaling, motor and cognitive function, and white matter integrity. RESULTS: ERCM contained a broad array of growth factors and demonstrated enhanced retention in CP-affected brain regions. In vitro, ERCM significantly reduced apoptos is and inflammation, and promoted oligodendrocyte maturation via upregulation of Nkx2.2, CN Pase, and MBP. In vivo, ERCM treatment improved motor and cognitive performance, in hibited cell death and inflammatory responses, and increased expression of oligodendrocyte markers, including Nkx2.2, Olig2, CNPase, and MBP via increasing growth factor expression. Furthermore, ERCM attenuated demyelination in the corpus callosum, a region particularly vulnerable in CP. CONCLUSION: ERCM confers therapeutic benefits in CP by preserving neural stem and oligodendrocyte progenitor cells, modulating apoptosis and inflammation, and enhancing oligodendrocyte differentiation. Accordingly, ERCM may present a good candidate as a CP therapeutic agent.