Intercellular mitochondrial transfer as a means of revitalizing injured glomerular endothelial cells

Abstract

BACKGROUND Recent studies have demonstrated that mesenchymal stem cells (MSCs) can rescue injured target cells via mitochondrial transfer. However, it has not been fully understood how bone marrow-derived MSCs repair glomeruli in diabetic kidney disease (DKD). AIM To explore the mitochondrial transfer involved in the rescue of injured glomerular endothelial cells (GECs) by MSCs, both in vitro and in vivo . METHODS In vitro experiments were performed to investigate the effect of co-culture with MSCs on high glucose-induced GECs. The transfer of mitochondria was visua lized using fluorescent microscopy. GECs were freshly sorted and ultimately tested for apoptosis, viability, mRNA expression by real-time reverse transcri ptase-polymerase chain reaction, protein expression by western blot, and mitochondrial function. Moreover, streptozotocin-induced DKD rats were infused with MSCs, and renal function and oxidative stress were detected with an automatic biochemical analyzer and related-detection kits after 2 wk. Kidney histology was analyzed by hematoxylin and eosin, periodic acid-Schiff, and immunohistochemical staining. RESULTS Fluorescence imaging confirmed that MSCs transferred mitochondria to injured GECs when co-cultured in vitro . We found that the apoptosis, proliferation, and mitochondrial function of injured GECs were improved following co-culture. Additionally, MSCs decreased pro-inflammatory cytokines [interleukin (IL)-6, IL-1β, and tumor necrosis factor-α] and pro-apoptotic factors (caspase 3 and Bax). Mitochondrial transfer also enhanced the expression of superoxide dismutase 2, B cell lymphoma-2, glutathione peroxidase (GPx) 3, and mitofusin 2 and inhibited reactive oxygen species (ROS) and dynamin-related protein 1 expression. Furthermore, MSCs significantly ameliorated functional parameters (blood urea nitrogen and serum creatinine) and decreased the production of malondialdehyde, advanced glycation end products, and ROS, whereas they increased the levels of GPx and superoxide dismutase in vivo . In addition, significant reductions in the glomerular basement membrane and renal interstitial fibrosis were observed following MSC treatment. CONCLUSION MSCs can rejuvenate damaged GECs via mitochondrial transfer. Additionally, the improvement of renal function and pathological changes in DKD by MSCs may be related to the mechanism of mitochondrial transfer.

Recent advances in regulating the proliferation or maturation of human-induced pluripotent stem cell-derived cardiomyocytes

“…Improved mitochondrial function has been observed in hiPSC-CMs following stimulation of maturation, but the mitochondria in these cells are not fully developed and incomparable to those of adult CMs [ 51 , 148 , 149 ], which might hinder their potential to acquire an adult-like phenotype. The development of methods involving intercellular mitochondrial transfer provides the possibility that transferring mitochondria from adult CMs into hiPSC-CMs might promote the generation of adult-like hiPSC-CMs [ 150 – 152 ]. Additionally, individual intervention strategies only promote one or several aspects of maturation, suggesting that maturation is driven by the coordinated regulation of multiple factors (Table 1 ).…”

Angiogenic activity of mitochondria; beyond the sole bioenergetic organelle

“…In the glomerular ECs, mitochondrial donation improved bioenergetic features like ΔΨm, ATP production, and proliferation, leading to the reduction of EC apoptosis. Under such conditions, transcription of dynamin-related protein 1 is diminished and ROS contents are reduced due to glutathione peroxidase, superoxide dismutase, Mfn, and B-2 cell lymphoma (Tang et al, 2022). The transfer of mitochondria via TNTs was also indicated during ischemia/ reperfusion injury that occurs from brain ECs, and pericytes to astrocytes to preserve blood-brain barrier (BBB) biological barrier (Figure 3) (Pisani et al, 2022a).…”

Mechanisms of Mitochondrial Influence on Tumor Radioresistivity

“…Mitochondrial transfer promotes cell survival including cardiomyocytes [14], virus infected cells [17], promotes brain regeneration after chemotherapy [19] or after cardiac arrest [54], repair injured glomerular endothelial cells [55] or promote bone formation [56].…”