bims-mitrat Biomed News
on Mitochondrial transplantation and transfer
Issue of 2025–03–30
seven papers selected by
Gökhan Burçin Kubat, Gulhane Health Sciences Institute
  1. Mitochondria transplantation transiently rescues cerebellar neurodegeneration improving mitochondrial function and reducing mitophagy in mice.
  2. Mitochondria-Rich Extracellular Vesicles from Bone Marrow Stem Cells Mitigate Muscle Degeneration in Rotator Cuff Tears in a Rat Model through Macrophage M2 Phenotype Conversion.
  3. Silicon Enhances Functional Mitochondrial Transfer to Improve Neurovascularization in Diabetic Bone Regeneration.
  4. Synergistic Modulating of Mitochondrial Transfer and Immune Microenvironment to Attenuate Discogenic Pain.
  5. Mitochondria derived from Stem cells modulated the biological behavior of monocyte-macrophages and inhibited inflammatory bone resorption.
  6. Direct exposure with exogenous mitochondria reduce colistin-induced mitochondrial dysfunction and cellular damages in isolated rat renal proximal tubular cells.
  7. Organoids as 3D Models for Studying Exogenous Mitochondrial Transplantation.
  1. Nat Commun. 2025 Mar 22. 16(1): 2839
    Mitochondria transplantation transiently rescues cerebellar neurodegeneration improving mitochondrial function and reducing mitophagy in mice.
    Shu-Jiao Li, Qian-Wen Zheng, Jie Zheng, Jin-Bao Zhang, Hui Liu, Jing-Jing Tie, Kun-Long Zhang, Fei-Fei Wu, Xiao-Dong Li, Shuai Zhang, Xin Sun, Yan-Ling Yang, Ya-Yun Wang.
      Cerebellar ataxia is the primary manifestation of cerebellar degenerative diseases, and mitochondrial dysfunction in Purkinje cells (PCs) plays a critical role in disease progression. In this study, we investigated the feasibility of mitochondria transplantation as a potential therapeutic approach to rescue cerebellar neurodegeneration and elucidate the associated mechanisms. We constructed a conditional Drp1 knockout model in PCs (PCKO mice), characterized by progressive ataxia. Drp1 knockout resulted in pervasive and progressive apoptosis of PCs and significant activation of surrounding glial cells. Mitochondrial dysfunction, which triggers mitophagy, is a key pathogenic factor contributing to morphological and functional damage in PCs. Transplanting liver-derived mitochondria into the cerebellum of 1-month-old PCKO mice improved mitochondrial function, reduced mitophagy, delayed apoptosis of PCs, and alleviated cerebellar ataxia for up to 3 weeks. These findings demonstrate that mitochondria transplantation holds promise as a therapeutic approach for cerebellar degenerative diseases.
    DOI:  https://doi.org/10.1038/s41467-025-58189-4
  2. Arthroscopy. 2025 Mar 25. pii: S0749-8063(25)00229-4. [Epub ahead of print]
    Mitochondria-Rich Extracellular Vesicles from Bone Marrow Stem Cells Mitigate Muscle Degeneration in Rotator Cuff Tears in a Rat Model through Macrophage M2 Phenotype Conversion.
    Xing Gao, Yuanyuan Chen, Jingzeng Wang, Jian Xu, Hu Wan, Xiao Li, Yulong Shi.
       PURPOSE: This study aimed to investigate the protective effects of extracellular vesicles derived from bone marrow stem cells (BMSC-EVs) on muscle degeneration in a rat model of rotator cuff tendon and suprascapular nerve (SSN) transection (termed the RCT-SSN model), focusing on mitochondrial transfer.
    METHODS: The EVs were identified and characterized. RCT-SSN model was established by transecting the supraspinatus, infraspinatus tendons, and suprascapular nerve. Ninety-six rats were divided into four groups (n=24 each): sham surgery, RCT-SSN treated with BMSC-EVs, RCT-SSN treated with EVs from Rhodamine-6G-pretreated BMSCs (Rho-EVs), or phosphate-buffered saline (PBS). Intramuscular injections were administered every two weeks. After 12 weeks, supraspinatus muscles were analyzed for atrophy, fibrosis, oxidative stress, macrophage phenotypes, serum cytokines, and mitochondrial characteristics. In vitro experiments included EVs tracking in macrophages, macrophage phenotype characterization, and inflammatory cytokine profiling.
    RESULTS: BMSC-EVs and Rho-EVs displayed similar morphology, but only BMSC-EVs contained functional mitochondria. BMSC-EVs significantly reduced muscle weight loss (0.047 ± 0.010% vs. 0.145 ± 0.013%, P < 0.001), increased muscle fiber cross-sectional area (2037 ± 231.9 μm2 vs. 527.9 ± 92.01 μm2, P < 0.001), and decreased fibrosis (12.09 ± 3.31% vs. 25.69 ± 4.84%, P < 0.001) compared to PBS. BMSC-EVs enhanced superoxide dismutase activity (93.3 ± 11.8 U/mg protein vs. 53.4 ± 8.0 U/mg protein, P < 0.001), improved mitochondrial function, density and structure, and induced an anti-inflammatory macrophage shift, suppressing proinflammatory cytokines in vitro and in vivo. Rho-EVs showed no such effects.
    CONCLUSIONS: This study showed that transecting the supraspinatus, infraspinatus tendons, and suprascapular nerve in a rat model induced muscle degeneration and fibrosis. BMSC-EVs, but not Rho-EVs, mitigated these effects by promoting an anti-inflammatory macrophage phenotype and protecting mitochondrial function through mitochondrial transfer.
    CLINICAL RELEVANCE: Mitochondrial transfer via BMSC-EVs may offer a therapeutic strategy to prevent muscle degeneration in rotator cuff tear patients.
    DOI:  https://doi.org/10.1016/j.arthro.2025.03.033
  3. Adv Sci (Weinh). 2025 Mar 24. e2415459
    Silicon Enhances Functional Mitochondrial Transfer to Improve Neurovascularization in Diabetic Bone Regeneration.
    Yu-Xuan Ma, Chen Lei, Tao Ye, Qian-Qian Wan, Kai-Yan Wang, Yi-Na Zhu, Ling Li, Xu-Fang Liu, Long-Zhang Niu, Franklin R Tay, Zhao Mu, Kai Jiao, Li-Na Niu.
      Diabetes mellitus is a metabolic disorder associated with an increased risk of fractures and delayed fracture healing, leading to a higher prevalence of bone defects. Recent advancements in strategies aim at regulating immune responses and enhancing neurovascularization have not met expectations. This study demonstrates that a silicon-based strategy significantly enhances vascularization and innervation, thereby optimizing the repair of diabetic bone defects. Silicon improves mitochondrial function and modulates mitochondrial fission dynamics in macrophages via the Drp1-Mff signaling pathway. Subsequently, functional mitochondria are transferred from macrophages to endothelial and neuronal cells through microvesicles, providing a protective mechanism for blood vessels and peripheral nerves during early wound healing. On this basis, an optimized strategy combining a silicified collagen scaffold with a Drp1-Fis1 interaction inhibitor is used to further regulate mitochondrial fission in macrophages and enhance the trafficking of functional mitochondria into stressed receptor cells. In diabetic mice with critical-sized calvarial defects, the silicon-based treatment significantly promotes vessel formation, nerve growth, and mineralized tissue development. These findings provide therapeutic insights into the role of silicon in promoting diabetic bone regeneration and highlight the importance of intercellular communication in diabetic conditions.
    Keywords:  bioactive silicon; diabetic bone defects; macrophages; mitochondrial transfer; neural; vascular
    DOI:  https://doi.org/10.1002/advs.202415459
  4. Adv Sci (Weinh). 2025 Mar 27. e2500128
    Synergistic Modulating of Mitochondrial Transfer and Immune Microenvironment to Attenuate Discogenic Pain.
    Xinzhou Wang, Zhenyu Guo, Linjie Chen, Jing Sun, Kenny Yat Hong Kwan, Morgan Jones, Yan Michael Li, Yangyang Hu, Xueqiang Wang, Pooyan Makvandi, Xiangyang Wang, Qiuping Qian, Yunlong Zhou, Aimin Wu.
      Discogenic pain, caused by intervertebral disc degeneration (IVDD), is a prevalent and challenging condition to treat effectively. Macrophage infiltration with neural ectopic in-growth resulting from structural disturbances within the intervertebral disc (IVD) is a major cause of discogenic pain. This work systematically reveals how nanoparticles can synergistically regulate the immune microenvironment and mitochondrial communication to attenuate discogenic pain. The antioxidant metal-polyphenol nanoparticle system can sequentially regulate macrophage phenotype and mitochondrial delivery efficiency. This strategy circumvents the necessity for mitochondrial isolation and preservation techniques that are typically required in conventional mitochondrial transplantation procedures. Furthermore, it facilitates the effective and sustained delivery of mitochondria to damaged cells. In vivo, this nanoparticle formulation effectively preserves the IVD height, maintains the structural integrity of the nucleus pulposus (NP), and restores pain thresholds. Thus, this nanoplatform offers an effective approach to traditional surgical treatments for discogenic pain, with significant potential for clinical application.
    Keywords:  discogenic pain; macrophage; mitochondrial transfer; nanoparticles
    DOI:  https://doi.org/10.1002/advs.202500128
  5. BMC Musculoskelet Disord. 2025 Mar 22. 26(1): 286
    Mitochondria derived from Stem cells modulated the biological behavior of monocyte-macrophages and inhibited inflammatory bone resorption.
    Xingfu Li, Jingyue Su, Xiang Liu, Wei Lu, Zhenhan Deng.
       BACKGROUND: The transfer of mitochondria from stem cells effectively attenuates the viability of inflammatory cells. However, there is a paucity of research supporting the inhibitory effect of stem cells on inflammatory bone resorption through mitochondrial transfer.
    METHODS: Mouse bone resorption models were established to investigate the impact of stem cell-derived mitochondria. Stem cells, stem cell-derived mitochondria and exosomes were injected into the animal models for experimental research. Healthy mice and mice with bone resorption were included as the control groups. The mitochondrial transfer and bone resorption of mice calvaria were evaluated by immunofluorescence, gross morphology, micro-computed tomography (micro-CT), immunohistochemical staining. Monocyte-macrophages were incubated with stem cell-derived mitochondria as experimental group. Monocyte-macrophages and activated monocyte-macrophages cultured separately served as the control groups. The mitochondrial transfer and biological behavior of monocyte-macrophages were evaluated by immunofluorescence, enzyme-linked immunosorbent assay (ELISA), Multiskan FC, and histochemical staining.
    RESULTS: Stem cell-derived mitochondria were successfully transferred to monocyte-macrophages. In vivo, local injection of stem cells, mitochondria, and exosomes effectively mitigated inflammatory cell infiltration, suppressed osteoclast maturation, and demonstrated a higher relative bone volume in mouse bone resorption models compared to the negative control group. In vitro, the co-incubation of mitochondria effectively suppressed the secretion of inflammatory cytokines, proliferation, fusion, and osteoclastogenesis in monocyte-macrophages compared to the control groups.
    CONCLUSIONS: The modulation of monocyte-macrophages biological behaviors by stem cells may occur through the transfer of mitochondria, thereby mitigating inflammatory bone resorption.
    Keywords:  Inflammatory bone resorption; Mitochondrial transfer; Stem cell
    DOI:  https://doi.org/10.1186/s12891-025-08529-8
  6. J Mol Histol. 2025 Mar 22. 56(2): 114
    Direct exposure with exogenous mitochondria reduce colistin-induced mitochondrial dysfunction and cellular damages in isolated rat renal proximal tubular cells.
    Abdollah Arjmand, Ahmad Salimi, Maryam Mohammadabadi, Mehrdad Faizi, Amir Fakhri, Zhaleh Jamali, Jalal Pourahmad.
      Kidney damage caused by colistin (polymyxin E) can bring about a decrease in creatinine clearance, potential proteinuria, cylindruria and oliguria in treated patients. It is therefore imperative to develop a new therapeutic strategy for reducing kidney damage after treatment with colistin. Mitochondrial damage is one of contributing factors in colistin-induced nephrotoxicity. Given the therapeutic benefits of mitochondrial transplantation by exogenous healthy mitochondria, we hypothesized that this strategy would be capable of ameliorating renal proximal tubular cells damage following exposure with colistin. For this purpose, we isolated rat renal proximal tubular cells (RPTCs) form kidney and exposed them with toxic concertation of colistin with/without rat healthy isolated mitochondria for 4 h. Cellular parameters such as lactate dehydrogenase (LDH), reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP), caspase 3 activation, lysosomal damage, glutathione and ATP content were measured. The results showed that administration of isolated mitochondria could improve colistin-induced nephrotoxicity and reduce mitochondrial dysfunction. Exogenous mitochondria reduced the activity of LDH, production of ROS, ATP and GSH depletion, loss of MMP, lysosomal damages and cell death. To the best of our knowledge, these results provide the first direct experimental evidence that direct exposure with exogenous mitochondria is capable of ameliorating cellular damage following treatment with colistin. These findings support that mitochondrial transplantation may be a promising therapeutic strategy for colistin-associated mitochondrial dysfunction in kidney cells.
    Keywords:  Antibiotic; Mitochondria; Mitochondria replenishment; Mitochondrial toxicity; Renal damage
    DOI:  https://doi.org/10.1007/s10735-025-10389-4
  7. Adv Exp Med Biol. 2025 Mar 26.
    Organoids as 3D Models for Studying Exogenous Mitochondrial Transplantation.
    Ismail Eş, Oner Ulger.
      Mitochondria play a critical role in cellular communication, cell proliferation, and apoptosis, which make them essential to maintaining cellular health. Recently, mitochondrial transplantation has emerged as a promising therapeutic approach to treat conditions such as ischemia, neurodegenerative diseases, and cardiovascular disorders by restoring mitochondrial function in damaged cells. Despite its potential, understanding mitochondrial behavior in vivo remains challenging; however, organoid models, which are three-dimensional structures derived from stem cells that mimic human tissues, offer a solution to study mitochondrial function and transplantation strategies under controlled conditions. These models are particularly necessary in studies, as they can replicate disease conditions and consequently enable researchers to investigate mitochondrial dynamics and therapeutic integration. Developing organoid systems optimized for mitochondrial transplantation requires exploring factors that influence mitochondrial uptake, refining transplantation strategies, and understanding their role in cellular regeneration in order to advance in the field of mitochondrial research.
    Keywords:  3D cell culture models; Delivery methods in organoids; Mitochondria; Mitochondrial transplantation; Organoids
    DOI:  https://doi.org/10.1007/5584_2025_857
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