bims-mitrat Biomed News
on Mitochondrial transplantation and transfer
Issue of 2026–03–01
ten papers selected by
Gökhan Burçin Kubat, Başkent Üni̇versi̇tesi̇
  1. From the energy factory to the intercellular communication medium: the emerging role of intercellular mitochondrial transfer and mitochondrial transplantation therapy in diabetes and diabetic complications.
  2. Mitochondria transfer in Glioblastoma.
  3. Nature-Inspired Surface Modification Strategy Reverses the Autophagic Flux Impairment of Mitochondrial Transplantation for Attenuating Ischemic Strokes.
  4. [Mitochondria in Cancer and Immunity].
  5. Comparative Analysis of Methodological Aspects of the Study of Extracellular Vesicles and Extracellular Mitochondria: From Isolation to Internalization.
  6. Nanotherapeutic strategy via ADSC-mitoEVs rescues ischaemic angiogenesis through mitophagy and mitochondrial metabolic reprogramming.
  7. Mitochondrial Transplantation from Bone Marrow Mesenchymal Stromal Cells Combined with Sildenafil Attenuated Vascular Remodeling and Improved Right Ventricular Dysfunction in Experimental Pulmonary Arterial Hypertension.
  8. An extracellular vesicle-mediated mitochondrial transfer network critical for testosterone synthesis.
  9. Mesenchymal Stromal Cells and Extracellular Vesicles: A Novel Therapeutic Paradigm for Mitochondrial Dysfunctions.
  10. Tunneling Nanotubes in Astrocyte-Neuron Crosstalk: From Intercellular Communication and Pathological Spread to Mechanobiological and Bio-Inspired Approaches.
  1. J Transl Med. 2026 Feb 25.
    From the energy factory to the intercellular communication medium: the emerging role of intercellular mitochondrial transfer and mitochondrial transplantation therapy in diabetes and diabetic complications.
    Dongze Li, Xiaolan Liu, Li Zhang, Qiming Gong, Wei Huang, Yong Xu.
      
    Keywords:  Diabetes; Diabetic complications; Mitochondrial dysfunction; Mitochondrial transfer; Mitochondrial transplantation
    DOI:  https://doi.org/10.1186/s12967-026-07868-x
  2. Neuro Oncol. 2026 Feb 23. pii: noag038. [Epub ahead of print]
    Mitochondria transfer in Glioblastoma.
    Simon Storevik, Mina Thue Augustsson, Shannon Moreino, Hanjo Köppe, Dionysios C Watson, Defne Bayik, Carolina De La Pena Fernandez, Amanda M Serapiglia, Nikhil Panicker, Justin Lathia, Hrvoje Miletic.
      Glioblastoma (GBM) is a highly aggressive and metabolically adaptable brain tumor characterized by profound cellular heterogeneity and therapy resistance. Recent research has uncovered the phenomenon of horizontal mitochondrial transfer (HMT) between GBM cells and their microenvironment, particularly astrocytes, which contributes to tumor progression, metabolic reprogramming, and treatment resistance. This review summarises current knowledge on mitochondrial exchange in GBM via tunneling nanotubes (TNTs), tumor microtubes (TMs) and potentially via extracellular vesicles (EVs). It also explores the functional consequences of HMT, including enhanced oxidative phosphorylation (OXPHOS), increased tumorigenicity, and altered therapeutic responses. This review highlights the need for further investigation into the molecular drivers and context-specific outcomes of mitochondrial transfer in GBM, with implications for novel therapeutic strategies.
    Keywords:  Glioblastoma; OXPHOS; mitochondria transfer; tumor microtubes; tunneling nanotubes
    DOI:  https://doi.org/10.1093/neuonc/noag038
  3. Adv Sci (Weinh). 2026 Feb 25. e18969
    Nature-Inspired Surface Modification Strategy Reverses the Autophagic Flux Impairment of Mitochondrial Transplantation for Attenuating Ischemic Strokes.
    Nisha Wang, Qiyang Ding, Lei Shi, Ji Xia, Shuyue Zhang, Chenxin Jian, Yixiao Yan, Xiuhua Luo, Jiarui Wang, Ming Cheng, Yiqiong Jia, Hao Tian, Wei Gao.
      Mitochondrial transplantation has emerged as a promising therapeutic intervention for ischemic strokes (IS). Although previous studies have demonstrated the therapeutic breakthroughs of mitochondrial transplantation facilitated by advances in biotechnology, in-depth investigations into the exact mechanisms underlying its beneficial effects remain insufficient. Here, we investigate how exogenous mitochondria interact with recipient cells to optimize therapeutic protocols and improve outcomes. Emerging evidence indicates that exogenous mitochondria act as triggers of mitophagy via the PTEN-induced putative kinase 1 (PINK1)-Parkin pathway. However, excessive reactive oxygen species (ROS) generated during ischemia-reperfusion injury activate the receptor-interacting protein (RIP)1/RIP3 pathway, leading to the blockage of autophagic flux. Hence, we devised a novel mitochondrial transplantation platform (MLSR) that utilizes functionalized starch as a stable coating for exogenous mitochondria and enables the co-delivery of the antioxidant resveratrol through the helical structure of the starch. Following internalization by recipient neurons, the exogenous mitochondria rapidly initiate mitophagy, while resveratrol escapes from the lysosome to inhibit the ROS-RIP1/RIP3-exosome axis. Experimental results demonstrate that MLSR effectively triggers and maintains positive autophagic flux, thereby suppressing the release of undegraded autophagosomes in the form of exosomes and preventing proinflammatory crosstalk between neurons and microglia. Therefore, our findings provide important implications for renewing the therapeutic potential of mitochondrial transplantation.
    Keywords:  ROS‐RIP1/RIP3‐exosome axis; autophagic flux; mitochondrial transplantation; mitophagy
    DOI:  https://doi.org/10.1002/advs.202518969
  4. Gan To Kagaku Ryoho. 2026 Feb;53(2): 73-79
    [Mitochondria in Cancer and Immunity].
    Takahiro Taki, Teruya Morinaga, Yosuke Togashi.
      Mitochondria are multifunctional organelles responsible not only for ATP production via oxidative phosphorylation but also for a wide range of cellular activities, including biosynthesis, redox regulation, signal transduction, and the control of apoptosis. In both cancer and immune cells, mitochondrial function plays various roles that extend beyond mere energy production. While cancer cells are known for the Warburg effect‒an enhanced glycolysis even in the presence of oxygen-they also actively utilize mitochondrial metabolism to fuel tumor progression. Furthermore, mutations in mitochondrial DNA(mtDNA) and alterations in nuclear genes encoding mitochondrial proteins contribute to tumorigenesis through various mechanisms, such as epigenetic modifications and the evasion of apoptosis. In immune cells, such as T cells and macrophages, mitochondrial metabolism is crucial for their differentiation and functional regulation. Key processes such as T cell activation, memory formation, and exhaustion, as well as macrophage functional polarization and inflammatory responses, are tightly linked to mitochondrial functional states. Recently, intercellular mitochondrial transfer within the tumor microenvironment has emerged as a significant phenomenon. Cancer cells can acquire mitochondria from surrounding cells to enhance their metabolic capacity and therapeutic resistance. Conversely, the transfer of mitochondria from cancer cells to T cells has been shown to suppress antitumor immune responses through metabolic dysfunction and homoplasmic replacement of T cell mtDNA. Based on these findings, therapeutic strategies targeting mitochondria are under investigation. These include inhibiting mitochondrial metabolism in cancer cells, boosting mitochondrial metabolism in T cells, and blocking intercellular mitochondrial transfer. Although preclinical studies have yielded promising results, further research is necessary to establish effective clinical therapies that can precisely modulate the complex metabolic interplay between cancer and immune cells.
  5. Curr Issues Mol Biol. 2026 Feb 16. pii: 217. [Epub ahead of print]48(2):
    Comparative Analysis of Methodological Aspects of the Study of Extracellular Vesicles and Extracellular Mitochondria: From Isolation to Internalization.
    Natalia Yunusova, Dmitry Svarovsky, Evgenya Kaigorodova, Alexey Dobrodeev, Virab Sisakian, Svetlana Tamkovich.
      Mitochondrial transfer in mammals has been proven to occur both under physiological conditions and during pathological conditions. It has been shown that neighboring cells can exchange mitochondria via nanotunnel tubes. However, there is evidence that free mitochondria, as well as whole mitochondria and individual mitochondrial fragments, can be transported between cells within extracellular vesicles (EVs). This review discusses the methodological aspects of isolation and a minimal set of methods for characterizing mitochondria-rich EVs (mitoEVs), as well as methodological approaches for studying the nucleic acid, protein, and lipid composition. It has been shown that mitoEVs, as well as extracellular mitochondria, contain a characteristic set of nucleic acids of mitochondrial origin. First and foremost, the dominant fraction of mitochondrial nucleic acids is mitochondrial DNA (mtDNA), a circular double-stranded molecule approximately 16.6 thousand base pairs in length. The mechanisms involved in EV internalization include clathrin-dependent endocytosis, caveolin-dependent endocytosis, raft-mediated endocytosis, and macropinocytosis. Mitochondrial-enriched autologous and xenogeneic EVs are thought to be internalized by similar mechanisms. The review also presents the main sources (stem cells, platelet concentrate, peripheral blood mononuclear cells) for obtaining mitochondria-rich EVs for therapeutic purposes.
    Keywords:  exosomes; extracellular mitochondria; internalization; mitochondria-rich extracellular vesicles; mitochondrial DNAs and RNAs; mitochondrial proteins; mitochondrial transfer; platelet concentrate; stem cells
    DOI:  https://doi.org/10.3390/cimb48020217
  6. J Nanobiotechnology. 2026 Feb 25.
    Nanotherapeutic strategy via ADSC-mitoEVs rescues ischaemic angiogenesis through mitophagy and mitochondrial metabolic reprogramming.
    Yuan-Zheng Zhu, Min-Chen Zhang, Xue-Er Li, Xing-Hong Zeng, Xue-Ting Gong, Yu-Zi Wu, Ze-Jun Dong, Shu Wu, Xue-Fei Liu, Abdul Haseeb Khan, Yang-Yan Yi.
      Ischaemic vascular diseases are critically linked to mitochondrial dysfunction in endothelial cells, which impairs angiogenesis and tissue repair. Although mitochondrial transplantation has emerged as a promising regenerative strategy, its clinical translation remains limited by inefficient delivery and poor retention in target tissues. Here, we demonstrate that mitochondrial-enriched extracellular vesicles derived from adipose-derived stem cells (ADSC-mitoEVs) function as an efficient cell-free nanotherapeutic that restores angiogenic function both in vitro and in a murine model of diabetic hindlimb ischaemia. Mechanistically, ADSC-mitoEV uptake triggers PINK1/Parkin-mediated mitophagy in recipient endothelial cells, a process essential for initiating angiogenesis. Moreover, ADSC-mitoEVs also directly deliver functional mitochondrial proteins, including superoxide dismutase 2 (SOD2), into the endogenous mitochondrial network, which enhances antioxidant activity and improves bioenergetic capacity independently of mitophagy, as demonstrated by reduced reactive oxygen species and elevated ATP production even in PINK1-silenced cells. Our findings establish ADSC-mitoEVs as a versatile cell-free nanotherapeutic that promotes mitochondrial quality control and metabolic reprogramming, offering a potent therapeutic avenue for ischaemic vascular diseases.
    Keywords:  Adipose-derived stem cells; Extracellular vesicles; Ischaemic vascular diseases; Mitochondrial transfer; Mitophagy
    DOI:  https://doi.org/10.1186/s12951-026-04183-x
  7. Int J Mol Sci. 2026 Feb 12. pii: 1761. [Epub ahead of print]27(4):
    Mitochondrial Transplantation from Bone Marrow Mesenchymal Stromal Cells Combined with Sildenafil Attenuated Vascular Remodeling and Improved Right Ventricular Dysfunction in Experimental Pulmonary Arterial Hypertension.
    Maria E de S F Onofre, Renata T Santos, Nazareth de N Rocha, Dayene de A F Caldeira, Johnatas D Silva, Carla M da Silva, Monique M Melo, Mayck M A da Silva, Clara R S Pastor, Julia D Batista, Isadora A Botelho, Rodrigo G Veras, Sabrina S de S Serra, Julianna D Zeidler, Patricia R M Rocco, Fernanda F Cruz, Pedro L Silva.
      Pulmonary arterial hypertension (PAH) is characterized by progressive vascular remodeling and right ventricular (RV) dysfunction, processes that are increasingly associated with disturbances in cellular metabolism. We investigated whether transplantation of exogenous mitochondria derived from bone marrow mesenchymal stromal cells, alone or combined with sildenafil, could improve mitochondrial homeostasis and attenuate cardiopulmonary remodeling in monocrotaline-induced PAH. Male Wistar rats were assigned to control (CTRL, n = 8) or PAH (n = 32) groups. Fourteen days after induction of PAH, animals were randomized to receive saline, sildenafil (20 mg/kg/day for 14 days), intravenous mitochondrial transplantation (100 μg, days 14 and 21), or combined therapy. On day 28, echocardiography, invasive measurement of RV systolic pressure (RVSP), pulmonary vascular histology, gene expression analyses (vimentin, VE-cadherin, and mitochondrial metabolism-related genes), and high-resolution respirometry were performed. All treatments significantly reduced RVSP compared with untreated PAH. Mitochondrial therapy, alone or combined with sildenafil, decreased arteriolar α-smooth muscle actin content, whereas endothelial-mesenchymal transition was attenuated only with combined treatment. Mitochondrial transplantation and sildenafil increased Complex I-dependent respiration, whereas Complex IV activity improved exclusively with mitochondrial therapy. Combined treatment reduced plasma IL-6 and IL-1β levels compared with PAH. Thus, mitochondrial transplantation, particularly when combined with sildenafil, improved RV function, limited pulmonary vascular remodeling, reduced plasma inflammatory markers, and changed key mitochondrial pathways in experimental PAH.
    Keywords:  cardiovascular function; metabolism; mitochondria; pulmonary arterial hypertension; vascular remodeling
    DOI:  https://doi.org/10.3390/ijms27041761
  8. Nat Cell Biol. 2026 Feb 27.
    An extracellular vesicle-mediated mitochondrial transfer network critical for testosterone synthesis.
    Kai Xia, Suyuan Zhang, Hao Peng, Hainan Chen, Cuifeng Yang, Jiajie Yu, Peng Luo, Qiying Lu, Hong Chen, Li Huang, Yifei Xiong, Lerong Zhao, Lei Jia, Lu Li, Yuan Qiu, Yan Guo, Congyuan Liu, Hang Fan, Ziran Dai, Guihua Liu, Qiong Ke, Tao Wang, Weiqiang Li, Lili Chen, Chunhua Deng, Haipeng Xiao, Andy Peng Xiang.
      Testosterone production by testicular Leydig cells (LCs) in male mammals is energetically demanding and prone to mitochondrial damage. Despite these challenges, LCs exhibit remarkable longevity and minimal turnover, suggesting the existence of specialized mechanisms that maintain LC mitochondrial homeostasis under such constrains. Here we identify a mitochondrial transfer network between LCs and different testicular macrophage (tMac) subpopulations. Leydig cells release extracellular vesicles containing defective mitochondria, which are eliminated by CD206hi tMacs in a TREM2-dependent process. Deletion of Trem2 in tMacs disrupts this transfer, leading to impaired testosterone synthesis. Conversely, LCs acquire extracellular vesicles containing functional mitochondria from MHCIIhi tMacs through ITGβ1-VCAM1 interactions. Loss of Vcam1 in LCs hinders this mitochondrial transfer, thereby compromising testosterone production. Together, our findings reveal an unrecognized mitochondrial transfer network between LCs and tMacs that safeguards LC homeostasis and testosterone production, offering valuable insights into intercellular communication mechanisms that maintain tissue homeostasis.
    DOI:  https://doi.org/10.1038/s41556-026-01896-x
  9. Int J Mol Sci. 2026 Feb 19. pii: 1981. [Epub ahead of print]27(4):
    Mesenchymal Stromal Cells and Extracellular Vesicles: A Novel Therapeutic Paradigm for Mitochondrial Dysfunctions.
    Eman Salem Algariri, Fazlina Nordin, Min Hwei Ng, Izyan Mohd Idris, Norwahidah Abdul Karim, Gee Jun Tye, Wan Safwani Wan Kamarul Zaman.
      Mitochondrial dysfunction is a central pathological feature of a wide range of inherited and acquired disorders and is characterized by impaired oxidative phosphorylation, disrupted cellular energy metabolism, and excessive oxidative stress. Although advances in molecular diagnostics have improved disease recognition, effective disease-modifying therapies remain limited, and clinical outcomes are often suboptimal, highlighting the need for novel therapeutic strategies. Mesenchymal stromal cells (MSCs) and their extracellular vesicles (MSC-EVs) have emerged as promising candidates for targeting mitochondrial dysfunction due to their regenerative, immunomodulatory, and metabolic regulatory properties. In this review, we provide a comprehensive overview of recent in vitro and in vivo studies investigating the capacity of MSCs and MSC-EVs to restore mitochondrial function by enhancing mitochondrial respiration, improving cellular bioenergetics, and reducing oxidative stress across diverse disease models. We further discuss the underlying mechanisms involved, including mitochondrial transfer, delivery of functional mitochondrial components, and modulation of the cellular microenvironment. Finally, we highlight the key advantages, translational potential, and remaining challenges associated with MSC- and MSC-EV-based therapies for mitochondrial dysfunction.
    Keywords:  MSC-EVs; MSC-base therapy; exosomes; mitochondrial diseases; mitochondrial transfer; oxidative phosphorylation
    DOI:  https://doi.org/10.3390/ijms27041981
  10. Brain Sci. 2026 Jan 28. pii: 138. [Epub ahead of print]16(2):
    Tunneling Nanotubes in Astrocyte-Neuron Crosstalk: From Intercellular Communication and Pathological Spread to Mechanobiological and Bio-Inspired Approaches.
    Gustavo Dias, Lívia de Sá Hayashide, Bruna Pessoa, Luan Pereira Diniz, Bruno Pontes.
      Tunneling nanotubes (TNTs) are dynamic cell surface conduits that enable direct transfer of ions, signaling molecules, and organelles. They have emerged as a key mechanism of intercellular communication, complementing classical pathways such as synapses and paracrine signaling. In the central nervous system (CNS), TNTs exhibit a functional duality, particularly under aging and stress, where TNT-mediated exchange may shift from protective to maladaptive. On one hand, TNTs support homeostatic functions, ranging from mitochondrial transfer to stem cell-mediated rescue and astrocyte-neuron metabolic support. On the other hand, they facilitate the spread of prions and neurodegenerative protein aggregates, such as Tau and α-synuclein, with astrocytes playing a regulatory role. Despite rapid advances, TNT research faces challenges from conceptual heterogeneity and experimental standardization, especially in complex tissues such as the CNS. Recent mechanobiological and bio-inspired approaches, including force-based assays and three-dimensional culture models, provide new insights into TNT formation, stability, and cargo transport, extending beyond neural systems. This review offers an integrative synthesis of molecular, structural, and mechanobiological principles underlying TNT-mediated communication, emphasizing astrocyte-neuron crosstalk, while proposing validation criteria to support rigor, reproducibility, and cross-study comparability. TNTs thus emerge as dynamic, context-dependent interfaces with broad relevance to neurodegeneration, cancer, and biomedical applications.
    Keywords:  CNS; bio-inspired approaches; chemoresistance; intercellular communication; mechanobiology; nanomedicine; neurodegenerative diseases; tunneling nanotubes
    DOI:  https://doi.org/10.3390/brainsci16020138
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