Endothelial progenitor cell transplantation alleviated ischemic brain injury via inhibiting C3/C3aR pathway in mice

Abstract

Endothelial progenitor cell transplantation is a potential therapeutic approach in brain ischemia. However, whether the therapeutic effect of endothelial progenitor cells is via affecting complement activation is unknown. We established a mouse focal ischemia model ( n = 111) and transplanted endothelial progenitor cells into the peri-infarct region immediately after brain ischemia. Neurological outcomes and brain infarct/atrophy volume were examined after ischemia. Expression of C3, C3aR and pro-inflammatory factors were further examined to explore the role of endothelial progenitor cells in ischemic brain. We found that endothelial progenitor cells improved neurological outcomes and reduced brain infarct/atrophy volume after 1 to 14 days of ischemia compared to the control ( p < 0.05). C3 and C3aR expression in the brain was up-regulated at 1 day up to 14 days ( p < 0.05). Endothelial progenitor cells reduced astrocyte-derived C3 ( p < 0.05) and C3aR expression ( p < 0.05) after ischemia. Endothelial progenitor cells also reduced inflammatory response after ischemia ( p < 0.05). Endothelial progenitor cell transplantation reduced astrocyte-derived C3 expression in the brain after ischemic stroke, together with decreased C3aR and inflammatory response contributing to neurological function recovery. Our results indicate that modulating complement C3/C3aR pathway is a novel therapeutic target for the ischemic stroke.

Endothelial Progenitor Cell Transplantation Attenuated Synaptic Loss by Enhancing CR3 Dependent Microglial Phagocytosis in Mice

“…2B, p<0.05). Our previous study proved that EPC transplantation enhanced M2 phenotype of microglia related genes but reduced M1 phenotype related genes in the mouse brain [13]. We speculated that the increased microglia in the EPCs treated mice was M2 microglia.…”

“…but not affected C3aR expression after tMCAO [13]. We tried to clarify whether EPC transplantation affected the other crucial receptor of C3, CR3, to promote tissue recovery.…”

“…However, emerging evidence implicated that C3/CR3 signaling was an etiologic factor in neurodegeneration [12]. Our previous study proved that EPC transplantation inhibited astrocyte releasing the complement component C3 and regulated C3/C3aR pathway on microglia, attenuating in ammatory response and neurological function de cit after ischemic stroke [13]. Whether EPC transplantation affecting CR3 to regulate microglia activity and exert the therapeutic function remains unexplored.…”

Role of hyperbaric oxygen in glioma

“… 9 Cerebral organoids repair ischemic stroke brain injury, 10 glycyrrhizin prevents hemorrhagic transformation and improves neurological outcome in ischemic stroke 11 and exo-transplantation of endothelial-specificity progenitor cells reduced ischemia damage. 12 Compared with stroke, it is very difficult to cure the glioma, which is currently treated with surgical resection, accessorial radio-therapy or chemistry drugs therapy like generation II alkylating agent temozolomide (TMZ) are usually used after operation. 13 Despite a lot of therapy with many surgical resection times, radio-therapy and chemistry drugs therapy having effects, the curing effectiveness is not ideal because of high recurrence rates and being resistant to radio-therapy and chemistry drugs therapy.…”

Adiponectin-Transfected Endothelial Progenitor Cells Have Protective Effects After 2-Hour Middle-Cerebral Artery Occlusion in Rats With Type 2 Diabetes Mellitus

“…Endothelial progenitor cells (EPCs), which were first discovered in 1997 (9), are now recognized as playing a significant role in promoting neurovascular repair and improving long-term neurological function (10). EPCs reside primarily in the bone marrow and can be mobilized into the bloodstream when tissue ischemia occurs.…”