Journal
CLINICAL INTERVENTIONS IN AGING
Volume 14, Issue -, Pages 2261-2271Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/CIA.S223595
Keywords
ischemic stroke; inflammation; cord blood-derived multipotent stem cells; regulatory T-cells; inflammasomes
Categories
Funding
- Primary Research & Development Plan of Shandong Province [2016GSF121044]
- Nation Natural Science Foundation of China [81373635]
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Background: Manipulating the immune inflammatory response after cerebral ischemia has been a novel therapeutic strategy for ischemic stroke. This study attempted to investigate the effects of the transplantation of lymphocytes co-cultured with human cord blood-derived multipotent stem cells (HCB-SCs) on the inflammatory response in transient middle cerebral occlusion (tMCAO) rats. Methods: The tMCAO rats were subjected to the transplantation of lymphocytes co-cultured with HCB-SCs through tail vein injection. Infarct size and neurological deficits were measured at 48 hrs after stroke. Neurological deficits were assessed using Bederson's scoring system and tape removal test. Blood T cell flow cytometry was performed to measure the differentiation of regulatory T cells (Tregs). Western blot was used to detect the protein levels of inflammation-related molecules, apoptosis-related molecule, and signaling molecules in ischemic brain. TUNEL staining was performed to analyze cell apoptosis in ischemic cerebral cortex. Results: The transplantation of lymphocytes co-cultured with HCB-SCs significantly improved the neurological defects, reduced ischemic brain damage, and increased the proportion of peripheral CD4(+)CD25(+)Foxp3(+) Tregs. Meanwhile, the transplantation of co-cultured cells decreased the expression of NLRP3 inflammasome and associated factors, such as caspase-1 and IL-1 beta, and inhibited the activation of NF-kappa B, ERK and caspase-3 in ischemic brain. The cocultured cells significantly decreased the number of tMCAO-induced cell apoptosis. Conclusion: Lymphocytes co-cultured with HCB-SCs exhibit a neuroprotective effect after ischemic stroke by promoting Tregs differentiation and suppressing NLRP3 inflammasome activation and neuron apoptosis, and might be a promising therapeutic strategy for ischemic stroke.
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