Abstract
Mitochondrial dysfunction has been linked to many diseases including organ degeneration and cancer. Mesenchymal stem cells/stromal cells (MSCs) provide a valuable source for stem cell-based therapy and represent an emerging therapeutic approach for tissue regeneration. Increasing evidence suggests that MSCs can directly donate mitochondria to recover from cell injury and rescue mitochondrial damage-provoked tissue degeneration. Meanwhile, cancer cells and cancer stromal cells also cross-talk through mitochondrial exchange to regulate cancer metastasis. This review summarizes the research on MSCs and their mitochondrial transfer. It provides an overview of the biology, function, niches and signaling that play a role in tissue repair. It also highlights the pathologies of cancer growth and metastasis linked to mitochondrial exchange between cancer cells and surrounding stromal cells. It becomes evident that the function of MSC mitochondrial transfer is a double-edged sword. MSC mitochondrial transfer may be a pharmaceutical target for tissue repair and cancer therapy.
Highlights
Mitochondria are well known as biological engines that generate energy
They decompose carbohydrates to produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS), providing most of the energy needed for metabolism and movement in living organisms [1,2]
Mitochondria transfer from mesenchymal stem cell/stromal cell (MSC) to astrocytes was stimulated by oxidative stress with an increased reactive oxygen species (ROS) level, and the transfer to neuron-like cells recovered cellular aerobic respiration and proliferation
Summary
Mitochondria are well known as biological engines that generate energy. They decompose carbohydrates to produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS), providing most of the energy needed for metabolism and movement in living organisms [1,2]. Apoptosis of ischemic endothelial cells (ECs) was reduced following mitochondrial transfer from BM-MSCs to HUVECs. human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) and BM-MSCs can both deliver mitochondria to mice cardiomyocytes with doxorubicin-induced damage, iPSC-MSCs have demostrated a higher transfer efficiency than BM-MSCs [21]. Mitochondria transfer from MSCs to astrocytes was stimulated by oxidative stress with an increased ROS level, and the transfer to neuron-like cells recovered cellular aerobic respiration and proliferation. Extracellular vesicles from human MSCs have shown a therapeutic effect on severe pneumonia in mice, possibly by the transfer of mitochondria or the mRNA of key mitochondrial genes [52]. Studies in hormonal therapy-resistant metastatic breast cancer have shown that horizontal transfer of mtDNA via extracellular vesicles plays a role in an exit from dormancy of cancer stem-like cells and leads to endocrine therapy resistance [60]. The mechanism is related to increased electron transport chain activity, reduced the level of reactive oxygen free radicals and prevention of apoptosis and necrosis [67]
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