bims-mitrat Biomed News
on Mitochondrial transplantation and transfer
Issue of 2026–05–17
seven papers selected by
Gökhan Burçin Kubat, Başkent Üni̇versi̇tesi̇
  1. Therapeutic Impact of Mitochondrial Transplants for Cardiovascular Diseases.
  2. Mitochondrial transfer technologies with molecular insights into clinical applications.
  3. Mitochondrial Transfer: A Novel Mechanism in the Development of Obesity and Obesity-Related Metabolic Diseases.
  4. Therapeutic potential of mitochondrial transfer in reversing mutant-to-wild-type mtDNA ratio and improving mitochondrial dysfunction in 1555A>G mtDNA mutation-associated hearing loss.
  5. Mitochondrial transfer from adipose-derived stem cells reprograms macrophage lipid metabolism to improve fat graft survival.
  6. Autologous bone marrow mesenchymal stem cell mitochondrial transplantation in recurrent assisted reproductive technology failure: a randomized controlled trial.
  7. Transplantation of encapsulated mitochondria alleviates dysfunction in mitochondrial and Parkinson's disease models.
  1. Int J Mol Sci. 2026 Apr 30. pii: 4018. [Epub ahead of print]27(9):
    Therapeutic Impact of Mitochondrial Transplants for Cardiovascular Diseases.
    Konstantina Antoniadou, Ioannis Shiammoutis, Christina Piperi.
      Mitochondria are vital organelles for human cells with fundamental roles in major metabolic processes such as calcium homeostasis, ATP production, apoptosis and signal transduction. Defective morphology and activity of these organelles have been tightly associated with the pathological onset of severe human disorders, including cardiovascular diseases. Targeting mitochondrial dysfunction has been an area of extensive research encompassing several approaches ranging from pharmacological agents to mitochondrial replacement techniques. Among them, mitochondrial transplantation has been a rapidly evolving approach, especially in the field of cardiovascular dysfunction for the restoration of injured or damaged myocardial cells. Various methods including tunneling nanotubes, nanoblade and "mitopunch" ensure the effective mitochondrial transfer from the donor to the recipient cell, with the internalization of the organelles, via endocytosis, enabling functional restoration. Results of preclinical and clinical trials involving mitochondrial transfer support the application of this technique in improving the function of the myocardium after damage caused by ischemia reperfusion injury. Herein, we discuss the beneficial role of mitochondrial transplantation in cardiovascular diseases and the current technical challenges of mitochondrial isolation, preservation, and targeted delivery, as well as their role in advancing precision medicine, offering a patient tailored therapeutic approach.
    Keywords:  CVD; ischemia/reperfusion injury; mitochondrial replacement therapy; mitochondrial transplantation; mtDNA
    DOI:  https://doi.org/10.3390/ijms27094018
  2. Stem Cells. 2026 May 07. pii: sxag026. [Epub ahead of print]
    Mitochondrial transfer technologies with molecular insights into clinical applications.
    Vahan Martirosian, Berney Peng, Michael A Teitell.
      Mitochondria are essential cell signaling, survival, and bioenergetic organelles that uniquely harbor a maternally inherited, multicopy genome called mitochondrial DNA (mtDNA). The occurrence or accumulation of mtDNA mutations underlies a spectrum of inherited and acquired mitochondrial syndromes and diseases and is increasingly recognized as a source of metabolic plasticity, clonal fitness, and therapy tolerance in cancer. Recent studies have revealed mitochondrial transfer as a potential mode of intercellular communication that could compensate for mtDNA mutation-associated mitochondrial dysfunction. Transfer of mitochondria can restore homeostasis in stressed recipient cells by rebuilding respiratory capacity, rebalancing redox state, and reshaping cell fate. Reported mechanisms of transfer include tunneling nanotubes, extracellular vesicles, cell fusion, and others, such as macropinocytosis. Here, we review and evaluate emerging technologies developed for mitochondrial transfer studies and define the impact of transfer on cell physiology and pathology. We discuss translational opportunities for mitochondrial transfer-based interventions, as well as how mitochondrial exchange may represent a new framework for understanding tumor heterogeneity, adaptation, and aggressiveness.
    Keywords:  Mitochondria; Mitochondrial transfer; mtDNA; techniques; transplantation
    DOI:  https://doi.org/10.1093/stmcls/sxag026
  3. Obesity (Silver Spring). 2026 May 11.
    Mitochondrial Transfer: A Novel Mechanism in the Development of Obesity and Obesity-Related Metabolic Diseases.
    Lei Zhu, Siyu Liang, Yuxing Zhao, Yi Hu, Fengying Gong, Huijuan Zhu.
      Obesity and its related metabolic diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD), represent a major global health challenge. Mitochondrial dysfunction is a key driver in their pathogenesis. This review explores the emerging role of mitochondrial transfer, a novel mode of cellular communication that can occur via tunneling nanotubes, extracellular vesicles, or as free mitochondria, in these conditions. Increasing evidence suggests that mitochondrial transfer may contribute to tissue homeostasis and metabolic adaptation, and that disruption of this process may participate in the pathogenesis of obesity and MASLD. In parallel, therapeutic strategies aimed at restoring mitochondrial function by enhancing endogenous mitochondrial transfer or through mitochondrial transplantation are beginning to emerge. This review summarizes current knowledge of the mechanisms underlying mitochondrial transfer, discusses roles in obesity and MASLD, and evaluates the therapeutic potential and translational challenges of targeting mitochondrial transfer in obesity and obesity-related metabolic disease.
    Keywords:  metabolic dysfunction‐associated steatotic liver disease; mitochondria transfer; mitochondrial therapy; obesity
    DOI:  https://doi.org/10.1002/oby.70223
  4. Sci Rep. 2026 May 13.
    Therapeutic potential of mitochondrial transfer in reversing mutant-to-wild-type mtDNA ratio and improving mitochondrial dysfunction in 1555A>G mtDNA mutation-associated hearing loss.
    Yujin Kim, Chang-Hee Kim, Dong Woo Nam, Bong Jik Kim, Ngoc-Trinh Tran, Jin Hee Han, Minyoung Kim, Shin-Hye Yu, Seo-Eun Lee, Jeong Seon Yeo, Iksun Kwon, Kyuboem Han, Chun-Hyung Kim, Young Cheol Kang, Byung Yoon Choi.
      Mitochondrial DNA (mtDNA) mutations are a major cause of sensorineural hearing loss (SNHL). The m.1555A >G mutation in the mitochondrial 12S rRNA gene is closely linked to nonsyndromic and aminoglycoside-induced hearing loss, leading to impaired oxidative phosphorylation (OXPHOS) and ATP production. Current treatments focus on auditory rehabilitation without addressing mitochondrial pathology. This study investigated mitochondrial transplantation as a therapeutic approach. Fibroblasts from two patients with homoplasmic m.1555A > G mutations identified during cochlear implant surgery received allogeneic mitochondria (PN-101) derived from human umbilical cord mesenchymal stem cells. Transplantation significantly increased intracellular ATP levels, complex I activity, and OXPHOS protein expression, while protecting against kanamycin-induced mitochondrial dysfunction. Importantly, PN-101 induced a heteroplasmy shift toward wild-type mtDNA, with repeated treatments sustaining and enhancing this effect. These findings demonstrate that PN-101-mediated mitochondrial transplantation improves mitochondrial bioenergetics and modulates mtDNA heteroplasmy in m.1555A > G mutant cells, suggesting a promising disease-modifying therapy for mtDNA-related hearing loss and a potential precision medicine approach.
    Keywords:  Hearing loss; Heteroplasmy; Mitochondrial transplantation; PN-101; mtDNA 1555A >G mutation
    DOI:  https://doi.org/10.1038/s41598-026-51402-4
  5. J Transl Med. 2026 May 14.
    Mitochondrial transfer from adipose-derived stem cells reprograms macrophage lipid metabolism to improve fat graft survival.
    Tingting Guo, Jiapeng Li, Jiani Lin, Mingli Xie, Yuyang Du, Jiayue Fu, Qing Wang, Xinyao Chen, Sai Luo.
       BACKGROUND: Autologous fat grafting is common for soft tissue repair, but often results in adipocyte necrosis due to ischaemia and hypoxia, causing inflammation and poor graft retention. Our research indicates that adipose-derived mesenchymal stem cells (ASCs) induce mitochondrial fatty acid β-oxidation (FAO) in macrophages, thus facilitating their M2 polarization and ultimately enhancing graft survival. ASCs also transfer mitochondria to recipient cells by tunnelling nanotubes (TNTs), increasing energy metabolism and the oxidative stress response. On the basis of these findings, we propose that ASCs facilitate mitochondrial transfer to macrophages through TNTs, which in turn enhances FAO, thus promoting M2 polarization and ultimately improving fat graft retention.
    METHODS: This study established a model of ASCs-assisted fat grafting in mice and an in vitro coculture system comprising ASCs and high-fat-treated macrophages. ASCs were treated with the actin polymerization inhibitor latrunculin A (latA) to block TNTs formation. We evaluated lipid deposition, mitochondrial transfer in macrophages, and mitochondrial function using electron microscopy, immunofluorescence, and qPCR.
    RESULTS: The findings indicated that ASCs enhance FAO in macrophages and improve fat graft retention, but latA pretreatment inhibited mitochondrial transfer, decreasing these effects.
    CONCLUSION: This research reveals a mechanism through which ASCs influence macrophage lipid metabolism through TNTs-mediated mitochondrial transfer, providing insights for enhancing fat graft survival.
    Keywords:  Adipose-derived stem cell; Fat transplantation; Macrophage; Mitochondrial fatty acid β-oxidation; Mitochondrial transfer; Tunnelling nanotubes
    DOI:  https://doi.org/10.1186/s12967-026-08224-9
  6. Stem Cell Res Ther. 2026 May 13.
    Autologous bone marrow mesenchymal stem cell mitochondrial transplantation in recurrent assisted reproductive technology failure: a randomized controlled trial.
    Xiaoping Liu, Dandan Wang, Lei Jia, Weixi Chen, Rui Huang, Cong Fang, Cijie Du, Liang Yang, Xingguo Liu, Xiaoyan Liang.
       BACKGROUND: Mitochondrial dysfunction contributes to poor embryo quality and recurrent assisted reproductive technology (ART) failure. Mitochondrial transplantation (MIT), which involves supplementing oocytes with exogenous mitochondria, has been proposed as a novel strategy to improve ART outcomes. However, both its clinical efficacy and safety remain unclear.
    METHODS: In this single-center trial, 151 patients with a history of ≥ 2 failed ART cycles provided 1178 metaphase II (MII) oocytes. Sibling oocytes were randomized 1:1 to receive autologous bone marrow mesenchymal stem cells (BMSCs) mitochondria co-injection during intracytoplasmic sperm injection (ICSI) or standard ICSI. The primary outcome was the rate of day-3 good-quality embryos.
    RESULTS: MIT significantly accelerated early embryonic cleavage at the 3-cell stage and 5-cell stage, but this morphokinetic alteration did not translate into improvements in good-quality embryo rate, clinical pregnancy rate, or live birth rate. Long-term follow-up of 23 live births revealed no adverse effects, with all offspring exhibiting normal growth and development. Exploratory analysis revealed that oocytes yielding ≥ 70% transferable embryos after MIT harbored an elevated higher burden of medium frequency (0.05-0.5) mtDNA point mutations.
    CONCLUSIONS: While autologous BMSCs-MIT transiently alters early cleavage kinetics, it does not demonstrate a clinical advantage in unselected patients with recurrent ART failure. Nevertheless, its observed safety profile and the identification of mtDNA mutation burden as a potential predictive biomarker provide a foundation for shifting future MIT research from a universal approach toward precision application in molecularly stratified populations. Trial registration ClinicalTrials.gov registration: NCT03639506.
    Keywords:  Autologous bone marrow mesenchymal stem cells; Embryo quality; Mitochondrial transplantation; Recurrent ART failure
    DOI:  https://doi.org/10.1186/s13287-026-05059-5
  7. Cell. 2026 May 14. pii: S0092-8674(26)00521-0. [Epub ahead of print]
    Transplantation of encapsulated mitochondria alleviates dysfunction in mitochondrial and Parkinson's disease models.
    Shiwei Du, Qi Long, Yanshuang Zhou, Jiangqin Fu, Hao Wu, Liang Yang, Yaohang Xie, Yingzhe Ding, Maolei Zhang, Jingyi Guo, Mengfei Wang, Jiajun Lin, Mingli Hu, Jian Zhang, Deyang Yao, Wei Li, Feixiang Bao, Ge Xiang, Yi Wu, Yile Huang, Haozhao Liang, Rui Wang, Heying Li, Baodan Chen, Chong Li, Junwei Wang, Jiwei Zhang, Dajiang Qin, Jianwei Sun, Yun Zhu, Fei Sun, Wuming Wang, Gang Lu, Wai-Yee Chan, Hui Zhao, Chenli Liu, Xingguo Liu.
      
    DOI:  https://doi.org/10.1016/j.cell.2026.05.004
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