bims-mitrat 2026-08-30 papers

bims-mitrat

Biomed News

on Mitochondrial transplantation and transfer

Issue of 2026–08–30
six papers selected by
Gökhan Burçin Kubat, Başkent Üni̇versi̇tesi̇

Mitochondria and exosome intercellular co-transfer via annular gap junction vesicles in the human glioblastoma stem cell niche.
Emerging Roles of Extracellular Vesicle-Mediated Transfer of Mitochondrial and Mitochondrial Components in Cancer.
Intercellular Mitochondria Transfer in Lung Diseases: New Mechanisms, Risks, Therapeutic Boundaries.
Adipose Stem Cell Mitochondrial Transplantation in ART: From Biological Rationale to Clinical Milestone.
Mitochondrial transplantation for delirium superimposed on dementia: from pathogenic mechanisms to clinical translation challenges.
Mitochondria-derived peptide hydrogel augments mitochondrial transplantation for promoting cardiac repair via macrophage metabolic reprogramming.

Hum Cell. 2026 Aug 24. pii: 130. [Epub ahead of print]39(9):

Mitochondria and exosome intercellular co-transfer via annular gap junction vesicles in the human glioblastoma stem cell niche.

Gabriel Arismendi-Morillo.



Keywords:  Annular gap junction vesicles; Exosomes; Glioblastoma; Mitochondrial transfer

DOI:  https://doi.org/10.1007/s13577-026-01437-6
Cells. 2026 Aug 20. pii: 1502. [Epub ahead of print]15(16):

Emerging Roles of Extracellular Vesicle-Mediated Transfer of Mitochondrial and Mitochondrial Components in Cancer.

Yue Gu, Chen Gu, Runfang Pan, Baonian Liu.

  Extracellular vesicles (EVs) are crucial mediators of intercellular communication in the tumor microenvironment (TME) which facilitate the transfer of bioactive molecules including functional mitochondria and their integral components. This review summarizes the emerging role of EV-mediated mitochondrial transfer in cancer progression. We delineate the mechanisms governing the packaging of mitochondria and their constituents into EVs and subsequently highlight their multifaceted functions across various malignancies, including breast cancer, prostate cancer, blood malignancies, head and neck squamous cell carcinoma, digestive system cancers, etc. Mitochondrial cargo, such as intact mitochondria, mitochondrial DNA (mtDNA), and RNA (mtRNA), are shown to reconfigure metabolism, enhance bioenergetics, promote proliferation and invasion, induce drug resistance, and remodel TME by suppressing antitumor immunity. While previous reviews have predominantly focused on the role of mitochondrial transfer in individual cancers or specific systemic diseases, we made a comprehensive overview encompassing diverse cancer types. These findings suggest that EV-mediated mitochondrial cargo transfer represents a biological intercellular communication mechanism with implications for tumor progression and therapeutic resistance. It is worth noting that we also apply standardized evidence-grading frameworks (C1-C4) across cancer types to provide a critical assessment of the current evidence and identify key methodological gaps that must be addressed in future studies. Collectively, this review underscores the significance of EV-mediated mitochondrial transfer as an important biological process in cancer, presenting it as a promising frontier for novel diagnostic and therapeutic interventions.

Keywords:  cancer; extracellular vesicles; mitochondrial transfer; mtDNA

DOI:  https://doi.org/10.3390/cells15161502
Antioxid Redox Signal. 2026 Aug 26. 15230864261481713

Intercellular Mitochondria Transfer in Lung Diseases: New Mechanisms, Risks, Therapeutic Boundaries.

Jiwei Zhu, Xuan Lai, Wang Lv, Zihao Li, Jun Chen, Li Yu, Luming Wang, Jian Hu.

  Significance: Intercellular mitochondrial transfer (MT) is increasingly recognized as more than a mechanism of bioenergetic rescue. By modulating mitochondrial quality control, redox homeostasis, immune-cell metabolism, and cell-death susceptibility, MT may influence disease progression and therapeutic response in lung diseases.Recent Advances: Studies have shown that engineered enhancement of mitochondrial biogenesis and transfer can restore mitochondrial homeostasis and attenuate pulmonary fibrosis. In cancer, mitochondrial acquisition can enhance metastatic fitness, redox buffering, and immune escape, whereas directed MT to T cells can improve T-cell antitumor activity. Emerging evidence further links MT to the regulation of oxidative stress, ferroptosis sensitivity, and redox-dependent immune remodeling within the tumor microenvironment.Critical Issues: The biological consequences of MT remain highly context dependent. Transfer efficiency, persistence of transferred mitochondria, cargo quality, and long-term integration into recipient-cell mitochondrial networks remain insufficiently characterized. The same process may promote tissue repair in the injured lung while conferring metabolic advantages on malignant cells, thereby defining important therapeutic and safety boundaries.Future Directions: Future studies should clarify how mitochondrial cargo quality, recipient-cell identity, and microenvironmental state shape MT outcomes. Improved methods for tracking mitochondrial fate and assessing long-term functional integration will be essential for translating MT-based strategies into safe and effective clinical therapies. Antioxid. Redox Signal. 00, 000-000.

Keywords:  cancer therapy response; lung diseases; metabolic reprogramming; mitochondria transfer; mitochondria transplant

DOI:  https://doi.org/10.1177/15230864261481713
Cells. 2026 Aug 10. pii: 1438. [Epub ahead of print]15(16):

Adipose Stem Cell Mitochondrial Transplantation in ART: From Biological Rationale to Clinical Milestone.

Helaruwan Pasan Kumara Wijethunga Arachchilage, Sanath Udayanga Kankanam Gamage, Atsushi Morimoto, Yoshiharu Morimoto.

  Oocyte quality is the primary determinant of success in assisted reproductive technologies (ART), and mitochondrial dysfunction is increasingly recognized as a central mediator of poor oocyte competence across advanced maternal age, recurrent implantation failure, polycystic ovary syndrome, endometriosis, and obesity. Chemical interventions improve the mitochondrial microenvironment but cannot restore depleted mitochondrial mass, while heterologous mitochondrial replacement remains constrained by ethical, legal, and biological limitations. This review examines the biological basis for mitochondrial intervention in oocytes, evaluates chemical and cellular therapeutic approaches, and assesses the evidence for autologous Adipose Stem Cell-derived Mitochondria ENergy Transfer (ASCENT). Mitochondria govern oocyte ATP production, calcium-mediated meiotic integrity, and redox homeostasis, and their disruption contributes to aneuploidy, fertilization failure, and embryonic arrest. Among cellular interventions, autologous adipose-derived stem cell mitochondrial transplantation offers minimally invasive tissue accessibility, morphological compatibility with oocyte mitochondria, robust membrane potential, and a preclinically validated Mito-ICSI delivery platform. Notably, ASCENT is currently the only autologous approach for which safety across three consecutive offspring generations has been reported in a mammalian model, with primary maternal origin of offspring mtDNA confirmed. Together, preclinical efficacy, transgenerational safety, and human proof-of-concept support progression toward a rigorously designed clinical trial, while ASC-derived mitochondria hold broader relevance in regenerative medicine.

Keywords:  Adipose Stem Cell Energy Transfer (ASCENT); Mito-ICSI; adipose-derived stem cells; autologous therapy; mitochondrial dysfunction; mitochondrial transplantation

DOI:  https://doi.org/10.3390/cells15161438
Front Aging Neurosci. 2026 ;18 1885815

Mitochondrial transplantation for delirium superimposed on dementia: from pathogenic mechanisms to clinical translation challenges.

Weiwei Hu, Yue He, Qiaoling Peng, Fang Sun.

  Delirium Superimposed on Dementia (DSD) is a common neuropsychiatric disorder in hospitalized elderly populations with poor prognosis, which can accelerate cognitive decline and increase mortality. Despite its clinical significance, there is a lack of effective therapeutic methods in clinical practice. Mitochondrial dysfunction, characterized by impaired energy metabolism, excessive reactive oxygen species (ROS) production and neuroinflammation activation, has been suggested as a potentially critical pathogenic link in DSD. As an emerging organelle-based therapy, mitochondrial transplantation (MTT) restores cellular energy homeostasis and mitigates oxidative stress by delivering functional mitochondria into damaged cells, thus holding promising potential as a future strategy for DSD treatment. This review systematically summarizes the hypothesized pathological role of mitochondrial dysfunction in DSD and the technical system of MTT, including mitochondrial isolation, purification, preservation and delivery strategies. We further elaborate on the plausible neuroprotective mechanisms of MTT and its preclinical evidence in neurodegenerative disease models relevant to, but distinct from, DSD. Additionally, we comprehensively analyze the technical, immunological and clinical challenges of MTT in DSD treatment, and propose targeted solutions and future research directions. This review constructs a theoretical framework for the hypothetical translation of MTT from basic research to clinical application in DSD, and provides novel insights for the development of future etiological therapies for this devastating disorder.

Keywords:  delirium superimposed on dementia; mitochondrial dysfunction; mitochondrial transplantation; neurodegenerative diseases; neuroprotection

DOI:  https://doi.org/10.3389/fnagi.2026.1885815
Bioact Mater. 2027 Jan;67 458-476

Mitochondria-derived peptide hydrogel augments mitochondrial transplantation for promoting cardiac repair via macrophage metabolic reprogramming.

Hang Li, Yushan Zhang, Yifan Jian, Fang Fang, Wenbin Ouyang, Donglin Zhuang, Wenhao Ju, Rui Gao, Yu Gao, Shaoyang Kang, Pengxu Kong, Yuwei Li, Xiangbin Pan, Weiwei Wang, Zujian Feng.

  Myocardial infarction (MI) is characterized by severe oxidative stress, excessive inflammation, and profound mitochondrial dysfunction. Although mitochondrial transplantation offers therapeutic promise for MI, its clinical translation is severely hampered by the extreme fragility of donor mitochondria with rapid loss of functional viability after isolation. Here, inspired by the intrinsic cellular defense mechanisms against mitochondrial dysfunction, MOTS-c, a mitochondria-derived peptide (MDP), is selected and further conjugated with self-assembling peptide (Q11) to fabricate a hydrogel-based mitochondrial delivery system (MQgel@Mito) for cardiac repair after MI. It has been observed that MQgel significantly extends the survival of isolated mitochondria and maintains metabolic enzyme activity for at least 8 h. More importantly, MQgel not only shields donor mitochondria from oxidative stress and calcium overload, but also enhances mitochondrial internalization by macrophages through an adenosine 5'-monophosphate-activated protein kinase (AMPK)-dependent mechanism. Furthermore, MQgel@Mito facilitates metabolic reprogramming of macrophages by suppressing pro-inflammatory glycolysis and enhancing oxidative phosphorylation (OXPHOS), thereby attenuating M1 polarization. Additionally, MQgel@Mito maintains mitochondrial homeostasis, reduces reactive oxygen species (ROS), and rescues apoptosis of macrophages. In a rat MI model, MQgel@Mito reduces M1 macrophage infiltration and cardiomyocyte damage by delivering viable mitochondria, thereby improving cardiac function and limiting pathological remodeling. These findings establish a paradigm for mitochondrial protection and demonstrate macrophage immunometabolism as a viable therapeutic strategy for MI.

Keywords:  Cardiac repair; Hydrogel; Mitochondrial transplantation; Myocardial infarction; Peptide

DOI:  https://doi.org/10.1016/j.bioactmat.2026.06.010