Umbilical cord-derived mesenchymal stem cells (UC-MSCs) engraftment is a potential therapy for cerebral ischemic stroke. However, the harsh microenvironment induced by cerebral ischemia/reperfusion restricts the survival rate and therapeutic efficiency of the engrafted UC-MSCs. In this study, we explored whether small extracellular vesicles (EVs) derived from injured neuronal cells following exposure to cerebral ischemia/reperfusion insult affect the survival of transplanted UC-MSCs. To establish a simulation of cerebral ischemia/reperfusion microenvironment comprising engrafted UC-MSCs and neuronal cells, we cocultured EVs derived from injured N2A cells, caused by exposure to oxygen-glucose deprivation and reperfusion (OGD/R) insult, with UC-MSCs in a conditioned medium. Coculture of UC-MSCs with EVs exacerbated the OGD/R-induced apoptosis and oxidative stress. Suppression of EVs-release via knock-down of Rab27a effectively protected the UC-MSCs from OGD/R-induced insult. Moreover, hypoxia preconditioning not only elevated the survival of UC-MSCs but also improved the paracrine mechanism of injured N2A cells. Altogether, these results show that EVs from injured N2A cells exacerbates OGD/R-induced injury on transplanted UC-MSCs . Hypoxia preconditioning enhances the survival of the engrafted-UC-MSCs; hence, thus could be an effective approach for improving UC-MSCs therapy in ischemic stroke.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382764 | PMC |
| http://dx.doi.org/10.1155/2020/9768713 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Single-Cell Insights Into Cellular Response in Abdominal Aortic Occlusion-Induced Hippocampal Injury.
CNS Neurosci Ther
January 2025
Beijing Key Laboratory of Hypoxia Translational Medicine, Xuanwu Hospital, Center of Stroke, Beijing Institute of Brain Disorder, Capital Medical University, Beijing, China.
Objective: Ischemia-reperfusion of the abdominal aorta often results in damage to distant organs, such as the heart and brain. This cellular heterogeneity within affected tissues complicates the roles of specific cell subsets in abdominal aorta occlusion model (AAO) injury. However, cell type-specific molecular pathology in the hippocampus after ischemia is poorly understood.
View Article and Find Full Text PDFOverexpressed CD73 attenuates GSDMD-mediated astrocyte pyroptosis induced by cerebral ischemia-reperfusion injury through the A2B/NF-κB pathway.
Exp Neurol
January 2025
Department of Neurosurgery, Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi 214000, China; Wuxi Medical Center of Nanjing Medical University, Wuxi 214000, China. Electronic address:
Ischemic stroke, resulting from the blockage or narrowing of cerebral vessels, causes brain tissue damage due to ischemia and hypoxia. Although reperfusion therapy is essential to restore blood flow, it may also result in reperfusion injury, causing secondary damage through mechanisms like oxidative stress, inflammation, and excitotoxicity. These effects significantly impact astrocytes, neurons, and endothelial cells, aggravating brain injury and disrupting the blood-brain barrier.
View Article and Find Full Text PDFNaotaifang formula regulates Drp1-induced remodeling of mitochondrial dynamics following cerebral ischemia-reperfusion injury.
Free Radic Biol Med
January 2025
Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China; Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, College of Medicine and Health Sciences, China Three Gorges University, Yichang, Hubei, China. Electronic address:
Cerebral ischemia-reperfusion injury (CIRI) has emerged as a hindrance for rehabilitation of ischemic stroke patients. Naotaifang (NTF) exhibits beneficial efficacy in alleviating inflammation and ferroptosis in vitro during CIRI. While the potential role of NTF in regulating mitochondrial dynamics in CIRI are not elucidated.
View Article and Find Full Text PDFDisruption of the Pum2 axis Aggravates neuronal damage following cerebral Ischemia-Reperfusion in mice.
Brain Res
January 2025
Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Institute of Stroke Research, Soochow University, Suzhou, 215006, China. Electronic address:
Stroke remains a leading cause of disability and mortality worldwide, with mitochondrial dysfunction closely linked to ischemic injury. This study explores the Norad-Pum2-Mff axis as a key regulator of mitochondrial function following ischemia-reperfusion (I/R) injury. Using an oxygen-glucose deprivation/reoxygenation (OGD/R) model, Mff protein levels were significantly elevated post-OGD/R, while mRNA levels remained unchanged, suggesting post-transcriptional regulation.
View Article and Find Full Text PDF[Neurocytoprotection advances in reperfusion therapy].
Zh Nevrol Psikhiatr Im S S Korsakova
January 2025
Pirogov Russian National Research Medical University (Pirogov University), Moscow, Russia.
Acute stroke is the second leading cause of death and the third leading cause of disability in the world. Ischemic stroke (IS) the most common type of stroke. In acute cerebral ischemia, damage to the brain tissue is complex and includes blood-brain barrier (BBB) dysfunction, neuroinflammation, oxidative stress, activation of intracellular and extracellular signaling pathways, expression of neurotoxic agents, excitotoxicity, and apoptosis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!