Intravenously Infusing the Secretome of Adipose-Derived Mesenchymal Stem Cells Ameliorates Neuroinflammation and Neurological Functioning After Traumatic Brain Injury.

Abstract

The secretome of mesenchymal stem cell (MSC) offers a series of immunoregulatory properties and is regarded as an effective method of mitigating secondary neuroinflammation induced by traumatic brain injury (TBI). The secretome of adipose-derived MSCs (ASC-ST) was collected under hypoxia conditions. Proteomics data were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and concentrations of major components were tested. After the TBI caused by an electric cortical contusion impactor, rats were injected ASC-ST through caudal veins for 7 days. The neurological functional prognosis of TBI rats was significantly improved, and the vasogenic edema of brain tissues that was measured 14 days after TBI was relieved by ASC-ST, corresponding to brain water content levels. ASC-ST ameliorated TBI-induced neuroinflammatory environments that caused the edema, the apoptosis of the neural cells, and the nerve fiber damage by increasing the number of M2 phenotypes present while reducing the number of M1 phenotype microglia present. Furthermore, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels were reduced, whereas transforming growth factor-beta (TGF-β) and tumor necrosis factor-stimulated gene 6 protein (TSG-6) levels were increased after secretome treatment. Altogether, ASC-ST is capable of improving neural functioning by modulating TBI-induced neuroinflammation and its related secondary insults. ASC-ST may be one of the most promising candidates for regulating the secondary inflammatory reactions of central nervous systems for clinical use.