Research Paper Volume 13, Issue 1 pp 262—278
Combined transplantation of neural stem cells and bone marrow mesenchymal stem cells promotes neuronal cell survival to alleviate brain damage after cardiac arrest via microRNA-133b incorporated in extracellular vesicles
- 1 Department of Emergency, The Second Affiliated Hospital of Kunming Medical University, Kunming 650000, Yunan Province, P.R. China
- 2 The 2nd Department of Hepatobiliary Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming 650000, Yunan Province, P.R. China
Received: March 3, 2020 Accepted: July 25, 2020 Published: January 12, 2021https://doi.org/10.18632/aging.103920
How to Cite
Copyright: © 2021 Li 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.
Neural stem cell (NSC) transplantation has prevailed as a promising protective strategy for cardiac arrest (CA)-induced brain damage. Surprisingly, the poor survival of neuronal cells in severe hypoxic condition restricts the utilization of this cell-based therapy. Extracellular vesicles (EVs) transfer microRNAs (miRNAs) between cells are validated as the mode for the release of several therapeutic molecules. The current study reports that the bone marrow mesenchymal stem cells (BMSCs) interact with NSCs via EVs thereby affecting the survival of neuronal cells. Hypoxic injury models of neuronal cells were established using cobalt chloride, followed by co-culture with BMSCs and NSCs alone or in combination. BMSCs combined with NSCs elicited as a superior protocol to stimulate neuronal cell survival. BMSCs-derived EVs could protect neuronal cells against hypoxic injury. Silencing of miR-133b incorporated in BMSCs-derived EVs could decrease the cell viability and the number of NeuN-positive cells and increase the apoptosis in the CA rat model. BMSCs-derived EVs could transfer miR-133b to neuronal cells to activate the AKT-GSK-3β-WNT-3 signaling pathway by targeting JAK1. Our study demonstrates that NSCs promotes the release of miR-133b from BMSCs-derived EVs to promote neuronal cell survival, representing a potential therapeutic strategy for the treatment of CA-induced brain damage.