Abstract
Stem cell-based therapy has been indicated to be beneficial for intervertebral disc regeneration. However, the underlying mechanisms have not been fully identified. The present study showed that bone marrow mesenchymal stem cells (BMSCs) donated mitochondria to adjacent nucleus pulposus cells (NPCs) in a coculture system. The mode of mitochondrial transfer between these cells was intercellular tunneling nanotube (TNT), which acted as a transportation expressway for mitochondria. NPCs acquired additional mitochondria from BMSCs in a concentration-dependent manner after rotenone-induced mitochondrial dysfunction in NPCs. Further research demonstrated that TNT-mediated mitochondrial transfer rescued NPCs from mitochondrial dysfunction and apoptosis, which was indicated by the recovery of the mitochondrial respiratory chain, the increase in mitochondrial membrane potential, and the decreases in reactive oxygen species (ROS) levels and apoptosis rates. Furthermore, Miro1, a critical protein that regulates mitochondrial movement, was knocked down in BMSCs and significantly reduced mitochondrial transfer from BMSCs to NPCs. These results suggested that Miro1 depletion inhibited the rescue of NPCs with mitochondrial dysfunction. Taken together, our data shed light on a novel mechanism by which BMSCs rescue impaired NPCs, providing a concrete foundation to study the critical role of intercellular interactions in disc regeneration.
Highlights
Stem cell-based therapy has great potential for the treatment of certain diseases [1]
We separated MitoTracker Red+ bone marrow mesenchymal stem cells (BMSCs) and CFSE+ nucleus pulposus cells (NPCs) in a Transwell system, and almost no MitoTracker Red+ NPCs were detected (Figures 1(e) and 1(f)). These results demonstrate that BMSCs are more capable of providing exogenous mitochondria to NPCs than neighboring NPCs in a coculture system
One study suggested that mitochondrial transfer reduces the apoptosis rate of NPCs when they were exposed to inflammatory factor [44]
Summary
Stem cell-based therapy has great potential for the treatment of certain diseases [1]. Mesenchymal stem cells (MSCs) have unique immunosuppressive properties and self-renewal and transdifferentiation abilities. MSCs may be used as candidate cells for disease treatment. MSCs can be obtained from the bone marrow (BMSCs), adipose tissue, and other sources. A series of clinical trials confirmed the beneficial effects of MSCs [2–4]. MSC-based tissue engineering is the main research direction for the regeneration of intervertebral discs [5, 6]. The mechanism underlying stem cell-based therapy is not understood. Intercellular interactions have attracted increasing attention as a novel mechanism underlying this therapy, and the transfer of organelles between cells has become the focus of many studies [7–9]
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