Treatment with Neuronal-Induced Human Mesenchymal Stem Cells Improves Functional Recovery of Acute Spinal Cord Injury through Attenuating Astrogliosis and Neurotoxic Astrocyte Activation

Vollständiger Abstract

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Objective : Most of the preclinical studies have been focusing on inhibition of astrogliosis which is known as a major mechanism that inhibits recovery from spinal cord injury (SCI). Although mesenchymal stem cells (MSCs) have been widely studied as therapeutic candidates for SCI treatment, the role of MSCs on astrogliosis remains unclear. Furthermore, recent studies revealed that astrogliosis also has a protective role in SCI. The purpose of this study was to determine whether neural-induced human adipose tissue-derived MSCs (NIhADSCs) promote SCI repair through astrogliosis modulation.Methods : NI-hADSCs were transplanted into the perilesional spinal cord in an acute severe SCI rat model. Functional recovery was evaluated serially on postoperative day 1 and weekly thereafter for 6 weeks using the Basso-Beattie-Bresnahan (BBB) locomotor rating scale. Western blot analysis was performed to assess protein levels of gliosis markers and neuroinflammatory pathways at 6 weeks post-injury. Histopathological examination was conducted at 6 weeks post-injury to evaluate astrogliosis and astrocyte phenotypic changes.Results : NI-hADSC transplantation significantly improved functional recovery compared with the SCI group, as demonstrated by a greater cumulative BBB locomotor score over 6 weeks (area under the curve : 23.65 vs. 13.58; p=0.026). At 6 weeks post-injury, the levels of glial fibrillary acidic protein (0.52±0.11 vs. 1.00±0.12; p=0.012), vimentin (0.54±0.01 vs. 1.00±0.08; p=0.006), and complement component 3 (C3; 0.38±0.05 vs. 1.00±0.07; p