ROS-responsive exogenous functional mitochondria can rescue neural cells post-ischemic stroke

Area of Science:

• Neuroscience
• Cell Biology
• Regenerative Medicine

Background:

• Mitochondrial transfer from mesenchymal stem cells (MSCs) shows therapeutic potential for neural cells post-ischemic stroke.
• Understanding which neural cells internalize mitochondria and the underlying mechanisms is crucial for optimizing this therapy.

Purpose of the Study:

• To investigate the capacity of different neural cell types to internalize exogenous functional mitochondria from MSCs.
• To elucidate the role of reactive oxygen species (ROS) in mediating mitochondrial uptake by stressed neural cells.

Main Methods:

• Functional mitochondria (F-Mito) from umbilical cord-derived MSCs were labeled and administered to neural cells in vitro and in vivo models of ischemia-reperfusion (MCAO and OGD/R).
• Cell viability (CCK-8), intracellular ROS levels (DCFH-DA, MitoSOX), and mitochondrial uptake (Mitotracker, WGA) were analyzed.
• Pharmacological ROS modulation was employed using acetylcysteine.

Main Results:

• Neurons and endothelial cells demonstrated higher F-Mito internalization efficiency compared to astrocytes.
• Internalized F-Mito reduced host cell ROS levels and enhanced cell survival.
• Ischemia-induced ROS production positively mediated F-Mito internalization, with ROS inhibition decreasing uptake.

Conclusions:

• Neural cell type influences mitochondrial internalization efficiency.
• ROS generation is a key regulator of exogenous mitochondrial uptake in ischemic conditions.
• MSC-derived mitochondria represent a promising therapeutic strategy for ischemic stroke, with ROS modulation as a potential enhancement.