Stem cells (Dayton, Ohio) · 2022
Stroke-Induced Neurological Dysfunction in Aged Mice Is Attenuated by Preconditioning with Young Sca-1+ Stem Cells.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Wlodarek Lukasz, Alibhai Faisal J, Wu Jun, Li Shu-Hong, Li Ren-Ke
Аннотация
AIMS: To date, stroke remains one of the leading causes of death and disability worldwide. Nearly three-quarters of all strokes occur in the elderly (>65 years old), and a vast majority of these individuals develop debilitating cognitive impairments that can later progress into dementia. Currently, there are no therapies capable of reversing the cognitive complications which arise following a stroke. Instead, current treatment options focus on preventing secondary injuries, as opposed to improving functional recovery.
METHODS: We reconstituted aged (20-month old) mice with Sca-1+ bone marrow (BM) hematopoietic stem cells isolated from aged or young (2-month old) EGFP+ donor mice. Three months later the chimeric aged mice underwent cerebral ischemia/reperfusion by bilateral common carotid artery occlusion (BCCAO), after which cognitive function was evaluated. Immunohistochemical analysis was performed to evaluate host and recipient cells in the brain following BCCAO.
RESULTS: Young Sca-1+ cells migrate to the aged brain and give rise to beneficial microglial-like cells that ameliorate stroke-induced loss of cognitive function on tasks targeting the hippocampus and cerebellum. We also found that young Sca-1+ cell-derived microglial-like cells possess neuroprotective properties as they do not undergo microgliosis upon migrating to the ischemic hippocampus, whereas the cells originating from old Sca-1+ cells proliferate extensively and skew toward a pro-inflammatory phenotype following injury.
CONCLUSIONS: This study provides a proof-of-principle demonstrating that young BM Sca-1+ cells play a pivotal role in reversing stroke-induced cognitive impairments and protect the aged brain against secondary injury by attenuating the host cell response to injury.
METHODS: We reconstituted aged (20-month old) mice with Sca-1+ bone marrow (BM) hematopoietic stem cells isolated from aged or young (2-month old) EGFP+ donor mice. Three months later the chimeric aged mice underwent cerebral ischemia/reperfusion by bilateral common carotid artery occlusion (BCCAO), after which cognitive function was evaluated. Immunohistochemical analysis was performed to evaluate host and recipient cells in the brain following BCCAO.
RESULTS: Young Sca-1+ cells migrate to the aged brain and give rise to beneficial microglial-like cells that ameliorate stroke-induced loss of cognitive function on tasks targeting the hippocampus and cerebellum. We also found that young Sca-1+ cell-derived microglial-like cells possess neuroprotective properties as they do not undergo microgliosis upon migrating to the ischemic hippocampus, whereas the cells originating from old Sca-1+ cells proliferate extensively and skew toward a pro-inflammatory phenotype following injury.
CONCLUSIONS: This study provides a proof-of-principle demonstrating that young BM Sca-1+ cells play a pivotal role in reversing stroke-induced cognitive impairments and protect the aged brain against secondary injury by attenuating the host cell response to injury.