Research Paper|Volume 12, Issue 11|pp 10931—10950

Hypoxia-preconditioned olfactory mucosa mesenchymal stem cells abolish cerebral ischemia/reperfusion-induced pyroptosis and apoptotic death of microglial cells by activating HIF-1α

Yan Huang^1,^2,³, Fengbo Tan⁴, Yi Zhuo^1,^2,³, Jianyang Liu⁵, Jialin He⁵, Da Duan^2,³, Ming Lu^1,^2,³, Zhiping Hu⁵

¹Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, P.R. China
²Department of Neurosurgery, Second Affiliated Hospital of Hunan Normal University, Changsha 410003, Hunan, P.R. China
³Hunan Provincial Key Laboratory of Neurorestoration, Second Affiliated Hospital of Hunan Normal University, Changsha 410003, Hunan, P.R. China
⁴Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, P.R. China
⁵Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, P.R. China

* Equal contribution

Received: January 5, 2020Accepted: March 30, 2020Published: June 7, 2020

Copyright © 2020 Huang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Microglial cells are the first line immune cells that initiate inflammatory responses following cerebral ischemia/reperfusion(I/R) injury. Microglial cells are also associated with a novel subtype of pro-inflammatory programmed cell death known as pyroptosis. Research has been directed at developing treatments that modulate inflammatory responses and protect against cell death caused by cerebral I/R. Key among such treatments include mesenchymal stem cell (MSC) therapy. A unique type of MSC termed olfactory mucosa mesenchymal stem cell (OM-MSC) confers neuroprotection by promoting the secretion of paracrine factors, and neuroprotection. This study investigated whether hypoxic OM-MSCs could inhibit microglial cell death upon I/R insult in vitro. A traditional oxygen-glucose deprivation/reperfusion (OGD/R) model, analogous to I/R, was established. Results showed that OGD/R induced apoptosis and pyroptosis in microglial cells while hypoxia in OM-MSCs significantly attenuated these effects. Moreover, the effects of OM-MSCs were mediated by Hypoxia-inducible factor 1-alpha (HIF-1α). Taken together, these findings reveal that hypoxia-preconditioned OM-MSC inhibits pyroptotic and apoptotic death of microglial cell in response to cerebral ischemia/reperfusion insult by activating HIF-1α in vitro.