bims-mitrat 2026-09-20 papers

bims-mitrat

Biomed News

on Mitochondrial transplantation and transfer

Issue of 2026–09–20
seven papers selected by
Gökhan Burçin Kubat, Başkent Üni̇versi̇tesi̇

Characterization of mesenchymal stromal cell-mediated mitochondrial transfer to healthy and diseased intervertebral disc cells.
Mitochondrial transfer: a novel paradigm for wound healing.
Myeloid cell replacement induces intercellular mitochondrial transfer and restores metabolism in a mouse model of mitochondrial disease.
Tunneling nanotubes regulate mitochondrial homeostasis between glioblastoma and astrocytes, and between tumor cells in vivo.
Mitochondrial remodeling by extracellular vesicles co-delivering functional mitochondria and a mitophagy inducer for neuropathic pain relief.
Mitochondrial transfer via ADSC-EVs reprograms glucose/glutamine metabolism to restore TCA cycle-driven M2 polarization in diabetic wounds.
The effects of hyperbaric oxygen therapy and mitochondrial transplantation on cisplatin toxicity.

PLoS One. 2026 ;21(9): e0357296

Characterization of mesenchymal stromal cell-mediated mitochondrial transfer to healthy and diseased intervertebral disc cells.

Ashley Cardenas, Noah Willett, Anthony Robayo, Jessica Berger, Blake Boadi, Chibuikem A Ikwuegbuenyi, Ibrahim Hussain, Roger Härtl, Lawrence J Bonassar.

Intradiscal injection of mesenchymal stromal cells has gained widespread interest for the treatment of intervertebral disc degeneration. Mesenchymal stromal cells have been shown to impart a therapeutic benefit on treated tissues through a variety of mechanisms including mitochondrial transfer. Mitochondrial transfer from mesenchymal stromal cells to diseased cells has been demonstrated, in numerous model systems, to increase the survival and function of recipient cells. To date there are few studies that have investigated mitochondrial transfer from mesenchymal stromal cells to intervertebral disc cells. The goal of this study is to characterize mitochondrial transfer from mesenchymal stromal cells to bovine and human intervertebral disc cells using confocal microscopy. Following a 24-hour coculture period, bovine mesenchymal stromal cells were shown to transfer mitochondria to bovine annulus fibrosus cells under both healthy and inflammatory conditions. In addition, human mesenchymal stromal cells were shown to transfer mitochondria to diseased, patient-derived intervertebral disc cells. Mitochondrial transfer quantity was found to increase under inflammatory stress conditions and with patient age, though functional consequences of this transfer remain to be determined. This study is the first to show mesenchymal stromal cells transfer mitochondria to bovine annulus fibrosus cells and patient derived intervertebral disc cells. We provide evidence that mitochondrial transfer is a relevant mechanism by which mesenchymal stromal cells communicate with intervertebral disc cells.

DOI: https://doi.org/10.1371/journal.pone.0357296
Burns Trauma. 2026 ;14 tkag043

Mitochondrial transfer: a novel paradigm for wound healing.

Yin He, Hong-Chao Huang, Lei Li, Si-Ya Wang, Guang-Yi Wang, Shi-Chu Xiao, Yong-Jun Zheng.

  Mitochondria not only serve as cellular powerhouses and metabolic regulatory hubs but also play crucial roles in calcium homeostasis, apoptosis regulation, and signal transduction. During wound repair, mitochondria modulate inflammatory and immune responses; drive angiogenesis; and supply energy for the proliferation, differentiation, and migration of repair cells such as fibroblasts and epithelial cells. When mitochondrial dysfunction exceeds the self-regulatory capacity, cellular energy deficits, metabolic disturbances, dysregulated signaling, and oxidative stress damage occur. These abnormalities collectively impair cellular repair mechanisms, ultimately contributing to chronic nonhealing wounds. Historically, mitochondria were thought to be acquired via vertical inheritance through cell division or mitochondrial biogenesis. However, the discovery of intercellular mitochondrial transfer provides novel insights into mitochondrial acquisition and presents new avenues for rescuing mitochondrial dysfunction. This article comprehensively reviews the dialectical relationship between mitochondrial dysfunction and impaired wound healing by integrating mechanisms of mitochondrial transfer, including modes, triggers, and regulatory pathways. It further highlights the therapeutic potential of mitochondrial transfer in wound repair. Additionally, this article provides forward-looking perspectives on clinical applications and future developments in mitochondrial transfer for wound healing, aiming to establish a theoretical foundation for mitochondrial transplantation therapies.

Keywords:  Mitochondria; Mitochondrial transfer; Mitochondrial transplantation; Wound healing

DOI:  https://doi.org/10.1093/burnst/tkag043
Nat Commun. 2026 Aug 15. pii: 9829. [Epub ahead of print]17(1):

Myeloid cell replacement induces intercellular mitochondrial transfer and restores metabolism in a mouse model of mitochondrial disease.

Hyunmin Cho, Ruhi Sayana, Abhishek Koladiya, Pasqualina Colella, Sangkyun Cho, James W S Jahng, Juan Jose Vasquez, Jessica Arozqueta Basurto, Joseph C Wu, Natalia Gomez-Ospina.

Friedreich's ataxia (FA) is a mitochondrial disease caused by frataxin deficiency that leads to progressive neurodegeneration and cardiomyopathy. Effective disease-modifying therapies remain limited. Here we show that myeloid cell replacement promotes neurological and cardiac recovery in FA mice through intercellular mitochondrial transfer. Donor-derived mitochondria are transferred from microglia and macrophages to central nervous system cells and cardiomyocytes, increasing oxidative phosphorylation and ATP synthesis gene expression and mitochondrial protein abundance. These molecular changes are accompanied by improved survival and growth in male and female mice and enhanced spontaneous locomotion, strength, coordination and cardiac and function in female mice. In cultured cells, mitochondrial transfer requires direct cell-cell contact and partially restores respiratory capacity in frataxin-deficient recipient cells, which exhibit enhanced mitochondrial uptake, suggesting disease-specific mechanisms that promote mitochondrial acquisition or retention. These findings identify mitochondrial transfer as a mechanism underlying the therapeutic effects of myeloid cell replacement and support hematopoietic transplantation for FA and other mitochondrial disorders.

DOI: https://doi.org/10.1038/s41467-026-76775-y
Nat Commun. 2026 09 15. pii: 9788. [Epub ahead of print]17(1):

Tunneling nanotubes regulate mitochondrial homeostasis between glioblastoma and astrocytes, and between tumor cells in vivo.

Ines Saenz-de-Santa-Maria, Anna Pepe, Jean-Yves Tinevez, Christel Brou, Yakov Vitrenko, Thomas Cokelaer, Elizabeth Cohen-Jonathan Moyal, Roberto Weigert, Chiara Zurzolo.

Tumor progression is driven by cancer cells' ability to establish a cellular network through tunneling nanotube-like connections (TNTs), which enable mitochondrial exchange both within the tumor cells and with the tumor microenvironment (TME). However, the functional consequences of mitochondrial transfer between tumor and non-tumor cells, and its occurrence in vivo, remain poorly understood. Here we show bidirectional mitochondrial transfer between Glioblastoma (GBM) cells and non-tumoral astrocytes (AS). We report that transfer of damaged mitochondria from GBM cells to AS is associated with activation of mitophagy in recipient cells, while astrocyte-derived mitochondria to GBM cells correlates with changes in mitochondrial activity and metabolic readouts. Furthermore, intravital subcellular microscopy (ISMic) in a live animal model allows the visualization of TNT connections with characteristics similar to those observed in vitro and supported TNT-mediated mitochondrial transfer in vivo. These findings reveal a potential mechanism of tumor adaptation and highlight TNTs as promising therapeutic targets.

DOI: https://doi.org/10.1038/s41467-026-76619-9
Mater Today Bio. 2026 Oct;40 103636

Mitochondrial remodeling by extracellular vesicles co-delivering functional mitochondria and a mitophagy inducer for neuropathic pain relief.

Xianquan An, Li Zhang, Xin Zhang, Meidan Fang, Cong Wang, Yu Han, Zheng Wang, Jinfeng Wang, Shuting Zuo.

  Neuropathic pain remains a major clinical challenge due to limited efficacy and tolerability of current treatments. Mitochondrial dysfunction in dorsal root ganglion (DRG) cells is recognized as a key pathogenic mechanism, but effective strategies to restore mitochondrial homeostasis are lacking. Here, we first identified profound deficits in mitochondrial quantity and quality in DRG neurons and satellite glial cells (SGCs) from a chemotherapy-induced peripheral neuropathy (CIPN) model. To address this, we developed an extracellular vesicle-based nanoplatform (EVs@Mi/UR) loaded with a mitophagy inducer, which integrates exogenous mitochondrial transplantation with mitophagy induction. EVs@Mi/UR not only increased mitochondrial mass in DRG neurons and SGCs through efficient mitochondrial transplantation, but also improved mitochondrial quality by eliminating damaged organelles, thereby enhancing mitochondrial respiration and metabolic function. In both CIPN and spared nerve injury (SNI) mouse models, EVs@Mi/UR significantly alleviated mechanical allodynia, thermal hyperalgesia, and cold hypersensitivity with superior efficacy. Notably, even in SNI models that did not exhibit baseline mitochondrial deficits, EVs@Mi/UR still produced analgesic effects by improving mitochondrial quality. This work establishes mitochondrial remodeling as a promising strategy for neuropathic pain and provides a translatable EV-based nanoplatform for dual-modality mitochondrial intervention.

Keywords:  Dorsal root ganglion; Extracellular vesicles; Mitochondrial transplantation; Mitophagy; Neuropathic pain

DOI:  https://doi.org/10.1016/j.mtbio.2026.103636
J Nanobiotechnology. 2026 Jul 28. pii: 859. [Epub ahead of print]24(1):

Mitochondrial transfer via ADSC-EVs reprograms glucose/glutamine metabolism to restore TCA cycle-driven M2 polarization in diabetic wounds.

Yue Zhang, Fei Han, Yixuan Yuan, Mengyang Li, Linbin Yi, Yujie Xiao, Dongliang Zhang, Zhi Zhang, Yunchuan Wang, Hongtao Wang, Dahai Hu.

  Chronic diabetic wounds are trapped in a persistent inflammatory state, largely due to macrophage failure to transition from pro-inflammatory (M1) to pro-reparative (M2) phenotypes. Here, we show that adipose-derived stem cell extracellular vesicles (ADSC-EVs) deliver functional mitochondria into diabetic wound macrophages, thereby restoring tricarboxylic acid (TCA) cycle-driven M2 polarization. Mechanistically, ADSC-EV-mediated mitochondrial transfer reactivates pyruvate dehydrogenase (PDH) and pyruvate carboxylase (PC), increases TCA cycle flux, and suggests enhanced glutamine anaplerosis, as evidenced by ¹³C-glucose isotope tracing. This metabolic rewiring restores oxidative phosphorylation (OXPHOS), elevates oxygen consumption rate (OCR) and suppresses glycolysis. Consequently, ADSC-EV treatment reduces M1 macrophages and increases M2 macrophages, lowers pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, MCP1, p < 0.0001), and upregulates IL-10 in vitro, p < 0.0001). In a diabetic mouse wound model, a single course of ADSC-EVs accelerates wound closure at day 14 (p < 0.05), enhances re-epithelialization and collagen deposition, and reduces local oxidative stress and inflammation. Mitochondria‑depleted Rho-ADSC-EVs show markedly diminished effects, confirming that functional mitochondrial transfer is the primary driver. Our findings establish ADSC-EV-mediated mitochondrial transfer as a central metabolic reprogramming strategy that breaks the inflammatory lock in diabetic wounds and promotes healing.

Keywords:  ADSC-EVs; Diabetic wound; Macrophages; Metabolic remodeling; Mitochondrial transfer; TCA cycle

DOI:  https://doi.org/10.1186/s12951-026-04846-9
Exp Mol Pathol. 2026 Sep 18. pii: S0014-4800(26)00055-9. [Epub ahead of print]148 105076

The effects of hyperbaric oxygen therapy and mitochondrial transplantation on cisplatin toxicity.

Volkan Tekin, Zehra Çiçek, Gizem Esra Koç, Mehmet Özler.

  Cisplatin is an effective chemotherapeutic agent with dose-limiting toxicity in non-target tissues. Hyperbaric oxygen therapy (HBOT) and mitochondrial transplantation (MitoTr) have been explored as supportive strategies in preclinical models. We examined whether HBOT and/or MitoTr modulate cisplatin-associated reductions in MTT metabolic activity and oxidative balance in healthy human mesenchymal stem cells (hMSCs) under incubator versus hyperbaric conditions. Bone marrow-derived hMSCs were seeded at 5 × 103 cells/well and exposed to cisplatin at an experimentally determined MTT-based LD50 (148 μM; 150 μM used). A delayed adjunctive intervention protocol was applied after LD50-level exposure: cisplatin or vehicle for 24 h, followed by 4 h MitoTr co-incubation (10× or 100× cell-number-scaled dose), then three HBOT sessions (90 min, 2.1 ATA) or matched incubator control. Endpoints were MTT absorbance (NAD(P)H-dependent oxidoreductase activity), total antioxidant status, total oxidant status, and oxidative stress index, analyzed by two-way ANOVA with Tukey post hoc. At 150 μM cisplatin, MTT absorbance was markedly reduced in all cisplatin-containing groups under both conditions (all p < 0.001 vs controls), and neither HBOT nor MitoTr restored MTT signal to control levels. Among cisplatin-free groups, M10 under HBOT exceeded control HB MTT absorbance (p = 0.009), whereas M10 under incubator conditions did not differ from control. HBOT reduced baseline MTT absorbance in cisplatin-free groups relative to matched incubator controls (p < 0.001). MitoTr lowered oxidant status under incubator conditions; HBOT improved redox indices in mitochondria-free groups. Under the LD50-level conditions tested, neither HBOT nor MitoTr restored NAD(P)H-dependent oxidoreductase (MTT) activity in hMSCs. Under non-toxic conditions, both modalities produced context-dependent redox changes. Whether lower, clinically relevant cisplatin exposures would yield partial protection remains an open question.

Keywords:  Cisplatin; Hyperbaric oxygen; Mesenchymal stem cells; Mitochondrial transplantation; Oxidative stress

DOI:  https://doi.org/10.1016/j.yexmp.2026.105076