bims-mitrat 2025-09-07 papers

bims-mitrat

Biomed News

on Mitochondrial transplantation and transfer

Issue of 2025–09–07
six papers selected by
Gökhan Burçin Kubat, Gulhane Health Sciences Institute

Vesicle-guided mitochondria: A new perspective for brain mitochondrial transplantation.
Light up the mitochondria: Smart tungstate-oligosaccharide nanoplatform orchestrates mitochondrial transfer from M2 macrophages to restore endothelial function for adaptive diabetic wound regeneration.
MIRO2-mediated mitochondrial transfer from cancer cells induces cancer-associated fibroblast differentiation.
From mitochondria to immune networks: new mesenchymal stem cell strategies to treat periodontitis.
Dysfunctional mitochondria in ageing T cells: a perspective on mitochondrial quality control mechanisms.
Exogenous Mitochondrial Pretreatment Enhances the Therapeutic Effect of UC-MSCs on NAFLD in Type 2 Diabetic Mice by Mediating Mitochondrial Transfer.

Ageing Res Rev. 2025 Aug 26. pii: S1568-1637(25)00227-2. [Epub ahead of print]112 102881

Vesicle-guided mitochondria: A new perspective for brain mitochondrial transplantation.

Antonella Girgenti, Laura Palumbo, Gokhan Burcin Kubat, Ibrahim Turkel, Pasquale Picone, Domenico Nuzzo.

  Mitochondrial activity is essential for the proper functioning of higher brain processes, and its impairment has been linked to a wide range of neurological disorders. Increasing evidence shows that under physiological and pathological conditions, mitochondria can be secreted into the extracellular environment to regulate various biological responses, including cellular bioenergetics. Today, the therapeutic modality known as "mitochondrial transplantation" has emerged as a cutting-edge and highly promising intervention for the promotion of cell and tissue regeneration. This innovative approach entails the replacement of dysfunctional mitochondria in the recipient organism with healthy, functional exogenous mitochondria, thereby aiming to restore cellular function and promote tissue repair and recovery. Several studies have demonstrated the beneficial effects of local or systemic administration of mitochondria on in vitro and in vivo models of brain diseases. We discuss the effect of mitochondrial transplantation in various brain diseases and highlight some critical issues. In this regard, we propose vesicles as a delivery system for both whole mitochondria and mitochondrial components to target cells in the central nervous system. Furthermore, the aim of this review is twofold: firstly, to emphasize the significance of brain mitochondrial transplantation, and secondly, to prompt the scientific community to consider the practical applications of brain mitochondrial transplantation. To this end, the text highlights the as yet unresolved issues and challenges that must be addressed and surmounted if this field is to progress. In conclusion, the authors express their support for the development of new potential therapies for mitochondrial diseases of the central nervous system.

Keywords:  Brain diseases; Mitochondrial dysfunction; Mitochondrial transplantation; Vesicles

DOI:  https://doi.org/10.1016/j.arr.2025.102881
Mater Today Bio. 2025 Oct;34 102196

Light up the mitochondria: Smart tungstate-oligosaccharide nanoplatform orchestrates mitochondrial transfer from M2 macrophages to restore endothelial function for adaptive diabetic wound regeneration.

Xiuhong Huang, Ziling Lin, Mingshu Ruan, Peizhen Huang, Hongmei Ding, Hao Pan, Jiahui Cao, Chunmei Ma, Qianhao Zhao, Wenping Guo, Keke Wu, Chongkai Fang, Aijun Liu, Liqin Zheng.

  Diabetic wound (DW) complications, driven by persistent oxidative stress, unresolved inflammation, and vascular dysfunction, present a critical clinical challenge. Given mitochondria's pivotal role in inflammatory regulation, intercellular mitochondrial transfer emerges as a promising therapeutic target for DW management. In this study, we engineered a ROS/glucose/pH-triple responsive nanoplatform (WOC) via coordination-driven assembly of tungstate anions (WO4 2-) and chitosan oligosaccharide (COS) to synchronize immunomodulation and angiogenesis for adaptive DW regeneration. The WOC platform demonstrated glucose/pH-triggered release of bioactive components with moderate ROS scavenging capacity, enabling real-time monitoring via visible colorimetric transition. By enhancing mitochondrial bioenergetics, WOC polarized macrophages to M2 phenotype and orchestrated vesicles-dependent mitochondrial transfer to injured endothelial cells, restoring vascular function through upregulated angiogenesis genes, enhanced migration, and tube formation. In diabetic rat models, WOC accelerated wound closure evidently, resolving inflammation and promoting scarless regeneration via balanced collagen deposition. This work establishes mitochondrial transfer as a promising strategy, offering a tunable nanotherapeutic approach to recalibrate cellular cross-talk and microenvironment dynamics in DW healing.

Keywords:  Angiogenesis; Diabetic wound; Macrophage; Mitochondria transfer; Tungstate-oligosaccharides nanoplatform

DOI:  https://doi.org/10.1016/j.mtbio.2025.102196
Nat Cancer. 2025 Aug 28.

MIRO2-mediated mitochondrial transfer from cancer cells induces cancer-associated fibroblast differentiation.

Michael Cangkrama, Huan Liu, Xiaoyu Wu, Josephine Yates, James Whipman, Christoph G Gäbelein, Mai Matsushita, Luca Ferrarese, Sibilla Sander, Francesc Castro-Giner, Simran Asawa, Magdalena K Sznurkowska, Manfred Kopf, Jörn Dengjel, Valentina Boeva, Nicola Aceto, Julia A Vorholt, Sabine Werner.

Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment that commonly support cancer development and progression. Here we show that different cancer cells transfer mitochondria to fibroblasts in cocultures and xenograft tumors, thereby inducing protumorigenic CAF features. Transplantation of functional mitochondria from cancer cells induces metabolic alterations in fibroblasts, expression of CAF markers and release of a protumorigenic secretome and matrisome. These features promote tumor formation in preclinical mouse models. Mechanistically, the mitochondrial transfer requires the mitochondrial trafficking protein MIRO2. Its depletion in cancer cells suppresses mitochondrial transfer and inhibits CAF differentiation and tumor growth. The clinical relevance of these findings is reflected by the overexpression of MIRO2 in tumor cells at the leading edge of epithelial skin cancers. These results identify mitochondrial transfer from cancer cells to fibroblasts as a driver of tumorigenesis and provide a rationale for targeting MIRO2 and mitochondrial transfer in different malignancies.

DOI: https://doi.org/10.1038/s43018-025-01038-6
Stem Cell Res Ther. 2025 Aug 29. 16(1): 470

From mitochondria to immune networks: new mesenchymal stem cell strategies to treat periodontitis.

Xinyu Wang, Chengran Wang, Mei Ren, Yingqi Shi, Tianqi Dong, Zirui Liu, Jinlan Jiang, Hongtao Wei.

  Periodontitis is a chronic inflammatory disease that damages periodontal tissues and is mainly caused by immune dysfunction. Current treatments, such as mechanical debridement and adjunctive antimicrobial, work poorly; periodontal surgery brings pain and complications.Mesenchymal stem cells (MSCs) have a powerful ability to regulate immune responses and great potential for tissue regeneration, thus attracting extensive attention in the field of periodontal treatment. However, in the microenvironment of chronic periodontal inflammation, the therapeutic effect of MSCs is severely inhibited. Recent studies show that MSCs can transfer mitochondria to change energy metabolism, thereby regulating immune cell differentiation and function, lowering local immune responses. Therefore, this review proposes an innovative strategy of treating periodontitis using mitochondrial transfer by MSCs. It explores how mitochondrial transfer helps restore energy metabolism, reduce oxidative stress, and regulate immune cell function. This approach may reshape the immune-metabolic network in the periodontal microenvironment, reduce local chronic inflammation, and promote periodontal tissue regeneration.With the development of new technologies, treatments based on mitochondrial transfer from MSCs are expected to become more accurate and efficient in future clinical applications. In addition, this review introduces the "organ-immune-metabolism" three-dimensional regeneration model, which integrates organ repair, immune regulation, and metabolic reprogramming. We hope this review may offer new therapeutic insights for researchers in oral biology and periodontists treating periodontitis and other immune-related diseases.

Keywords:  Immune regulation; Mesenchymal stem cells; Metabolism; Mitochondrial transfer; Periodontitis

DOI:  https://doi.org/10.1186/s13287-025-04619-5
EMBO Rep. 2025 Aug 29.

Dysfunctional mitochondria in ageing T cells: a perspective on mitochondrial quality control mechanisms.

Lin Luo, Ana Victoria Lechuga-Vieco, Clara Sattentau, Mariana Borsa, Anna Katharina Simon.

  Dysfunctional mitochondria are a hallmark of T cell ageing and contribute to organismal ageing. This arises from the accumulation of reactive oxygen species (ROS), impaired mitochondrial dynamics, and inefficient removal of dysfunctional mitochondria. Both cell-intrinsic and cell-extrinsic mechanisms for removing mitochondria and their byproducts have been identified in T cells. In this review, we explore how T cells manage mitochondrial damage through changes in mitochondrial metabolism, mitophagy, asymmetric mitochondrial inheritance, and mitochondrial transfer, highlighting the impact of these mechanisms on T cell ageing and overall organismal ageing. We also discuss current therapeutic strategies aimed at removing dysfunctional mitochondria and their byproducts and propose potential new therapeutic targets that may reverse immune ageing or organismal ageing.

Keywords:  Asymmetric Cell Division; Mitochondrial Metabolism; Mitochondrial Transfer; Mitophagy; T Cell Ageing

DOI:  https://doi.org/10.1038/s44319-025-00536-z
Stem Cells Int. 2025 ;2025 4639115

Exogenous Mitochondrial Pretreatment Enhances the Therapeutic Effect of UC-MSCs on NAFLD in Type 2 Diabetic Mice by Mediating Mitochondrial Transfer.

Ruofan Hu, Jian Zhao, Yu Cheng, Wanlu Su, Rui Ren, Haixia Zhang, Yue Zhang, Anning Wang, Yiming Mu, Songyan Yu.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease and is a comorbidity in type 2 diabetes (T2D) mellitus. Mesenchymal stem cell (MSC) is emerging as a potential therapeutic strategy for diabetes and NAFLD through mitochondrial transfer initiated by signaling from injured recipient cells. Thus, in this study, we investigated whether exogenous mitochondrial preconditioning of MSCs could exert superior effects on NAFLD and explore the role of MSCs-mediated mitochondrial transfer into hepatocyte. Methods: After free HepG2 mitochondria pretreated, umbilical cord-derived MSCs (UC-MSCs) (mito-MSCs), T2D model mice were infused with equal amounts of MSCs/mito-MSCs via the tail vein once a week for 4 weeks. Body weight and random blood glucose were monitored weekly. After the end of treatment, the mitochondrial transfer level of MSCs before and after pretreatment were monitored by fluorescence tracing. Blood and liver were collected for biochemical and histopathological examinations. The number, morphology, and function of mitochondria in liver tissue were evaluated by tissue electron microscopy and western blot analysis. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to monitor the expression of genes associated with lipid metabolism and regulation pathways. Results: Pretreatment of UC-MSCs enhanced the efficacy of MSCs in lowering blood glucose, liver transaminase, triglyceride levels, and reducing histological damage, which may be related to free mitochondria triggering autophagy of MSCs, which in turn promoted the entry of MSCs mitochondria into the liver tissue of diabetic mice. Conclusion: Exogenous mitochondria could enhance the therapeutic efficacy of MSCs in NAFLD via mediating mitochondrial transfer, which offers a novel strategy for the improving the outcomes of MSCs cell-therapy for diabetes-related NAFLD.

DOI: https://doi.org/10.1155/sci/4639115