bims-mitrat 2025-11-09 papers

Hepatobiliary Pancreat Dis Int. 2025 Oct 14. pii: S1499-3872(25)00172-9. [Epub ahead of print]

From preservation to repair: Mitochondrial transplantation as a paradigm shift in organ transplantation.

Emma Peveri, Timothy Sganga, Emilio Peveri, Adam Jones, Thomas Ritchey, Sandrine Lablanche, Kelsey Fisherwellman, Amish Asthana, Giuseppe Orlando, Quentin Perrier.

Organ transplantation faces a persistent mismatch between the number of available donor organs and the growing demand for transplants. Conventional preservation techniques primarily focus on delaying deterioration rather than actively restoring organ function, especially at the mitochondrial level, a key site of injury during ischemia-reperfusion. Mitochondrial transplantation, a novel regenerative strategy, offers a compelling solution by delivering viable mitochondria to damaged tissues ex vivo, particularly during machine perfusion. This approach not only improves bioenergetic recovery and reduces oxidative stress but also reconditions marginal organs to meet transplantation standards. Preclinical studies across heart, lung, and kidney models demonstrate the potential of mitochondrial transplantation to bridge preservation and repair, expanding the transplantable organ pool. This review highlights mitochondrial transplantation as a transformative intervention poised to reshape the future of organ preservation and transplant viability.

Keywords: Ex vivo; Ischemia-reperfusion injury; Mitochondria; Organ transplantation

DOI: https://doi.org/10.1016/j.hbpd.2025.10.003

Cell Mol Bioeng. 2025 Oct;18(5): 403-417

Surface-Engineered Mitochondria with Targeting Potential for Endothelial Repair.

Brandon Applewhite, Natalia Matiuto, Aurea Del Carmen, Bin Jiang.

Purpose: Mitochondrial dysfunction contributes to endothelial injury in vascular diseases and interventions. While mitochondrial transplantation offers a promising therapeutic strategy, current approaches lack target specificity, efficient uptake, and long-term retention. This study presents a surface-engineering approach to enhance mitochondria delivery to the vascular endothelium as a step toward novel endothelial repair strategies.
Methods: Mitochondria were isolated from healthy induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) and surface functionalized with a phospholipid-based coating platform (DSPE-PEG) to enable peptide functionalization. DSPE-PEG was conjugated to either VCAM-1-binding peptide and collagen-binding peptide to enable targeting to dysfunctional and injured endothelium. Mitochondria particle characteristics were measured using flow cytometry, dynamic light scattering and Seahorse. Mitochondrial uptake, retention, and function were assessed in human diabetic aortic endothelial cells (DAECs) using confocal microscopy, flow cytometry, JC-1 staining, and Seahorse metabolic analysis.
Results: iPSC-MSCs provided bioenergetically competent mitochondria suitable for therapeutic delivery. DSPE-PEG surface functionalization significantly enhanced mitochondrial uptake in DAECs, compared to uncoated mitochondria. Confocal imaging and quantitative analysis revealed increased cytoplasmic retention and greater colocalization with the endogenous mitochondrial network after 24 h. Functional assays demonstrated improved mitochondrial membrane potential and sustained oxygen consumption in recipient cells, indicating enhanced host mitochondrial function following treatment with surface-engineered mitochondria.
Conclusions: This study establishes a proof-of-concept for mitochondria surface engineering to enhance mitochondria transplantation to damaged endothelium, demonstrating improved cellular uptake and bioenergetic restoration. These findings provide a foundation for developing adaptable, cell-free therapeutics for vascular disease.
Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-025-00862-1.

Keywords: Bioenergetic restoration; Endothelial dysfunction; Lipid-polymer coatings; Mitochondrial transplantation; Surface engineering; Vascular regeneration

DOI: https://doi.org/10.1007/s12195-025-00862-1

STAR Protoc. 2025 Oct 30. pii: S2666-1667(25)00580-5. [Epub ahead of print]6(4): 104174

Protocol for mitochondria lipid encapsulation using a dual-tube system for mitochondria transfer therapy.

Gen Hamanaka, Dong Bin Back, Ester Licastro, Shin Ishikane, Takafumi Nakano, Kazuhide Hayakawa.

Mitochondria transplantation therapy is emerging as a novel therapeutic approach to promote neuroprotection in central nervous system (CNS) disorders. Here, we present a protocol for mitochondrial surface modification that enhances the restoration of intracellular adenosine triphosphate (ATP) levels under conditions of oxidative stress. We describe steps for isolating mitochondria, preparing the dual-tube system, and encapsulation with lipid coat. We then detail procedures for performing assays and analyses. For complete details on the use and execution of this protocol, please refer to Nakano et al.1.

Keywords: Metabolism; Neuroscience; cell Biology; tissue Engineering

DOI: https://doi.org/10.1016/j.xpro.2025.104174

Biol Pharm Bull. 2025 ;48(11): 1652-1666

Mitochondrial Activation and Therapeutics: Innovations in Cell- and Organelle-Specific Medicine.

Itsumi Sato, Masahiro Shiraishi, Kaede Norota, Kaoru Shiraki, Yuma Yamada.

Mitochondria are essential for cellular functions, including ATP production, calcium homeostasis, oxidative stress regulation, and apoptosis. Mitochondrial dysfunction is associated with a variety of diseases, including neurodegenerative disorders, skeletal muscle diseases, and mitochondrial diseases. This review explores the latest mitochondrial-targeted therapeutic approaches across the following key perspectives: (1) technological innovations in mitochondrial transplantation, focusing on tunnel nanotubes and extracellular vesicles; (2) the role of mitochondria in skeletal muscle diseases and therapeutic activation strategies; (3) advances in mitochondrial enhancement techniques within cell therapy, particularly in pediatric applications; and (4) the latest treatment modalities for mitochondrial diseases, such as gene and cell therapies. Taken together, these strategies demonstrate the transformative potential of mitochondrial targeting in cell- and organelle-specific medicine. Additionally, the MITO-Porter system is highlighted as an innovative drug delivery platform contributing to these advances.

Keywords: cell therapy; drug delivery system; mitochondria; mitochondrial disease; organelle medicine; skeletal muscle disease

DOI: https://doi.org/10.1248/bpb.b25-00218

World J Hepatol. 2025 Oct 27. 17(10): 110054

Mitochondrial transplantation and platelet rich plasma for the treatment of non-alcoholic fatty liver disease.

Manuel Alejandro Vargas-Vargas, Marcela González-Montoya, Olin Torres-Isidro, Omar Ortiz-Avila, Elizabeth Calderón-Cortés, Christian Cortés-Rojo.

Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent global health concern, contributing to the development of insulin resistance, diabetes, cardiovascular disease, cirrhosis, and hepatocellular carcinoma. Since no approved drugs for the treatment of NAFLD exist, there is an urgent need for novel therapeutic strategies. Two such strategies are mitochondrial transplantation and platelet rich plasma (PRP) therapy. In preclinical NAFLD, mitochondrial transplantation alleviates steatosis by improving the hepatic imbalance between fatty acid utilization and synthesis. Moreover, it reduces excessive reactive oxygen species production and lipid peroxidation, thereby reducing inflammation and fibrosis. In contrast, PRP therapy ameliorates hepatic damage induced by xenobiotics by deactivating stellate cells, reducing fibrosis and apoptosis, and decreasing inflammation via NF-κB inhibition, while enhancing antioxidant defenses. These effects may be related to the improvement of NAFLD observed in a preclinical study. We propose that a combination of mitochondrial transplantation and PRP therapy may represent a novel approach for treating NAFLD by targeting different aspects of NAFLD in a complementary manner. We discuss the limitations of these therapies, as preclinical studies addressing NAFLD with these therapies are scarce, and there are no clinical trials in humans.

Keywords: Cirrhosis; Electron transport chain; Hepatocyte; Inflammation; Mitochondria; Non-alcoholic fatty liver disease; Oxidative stress; Steatohepatitis; Steatosis; Tissue regeneration

DOI: https://doi.org/10.4254/wjh.v17.i10.110054

Sci China Life Sci. 2025 Nov 06.

Mitochondria beyond boundaries: from cellular powerhouses to intercellular messengers in health and disease.

Haixia Zhuang, Wenxin Mo, Jianming Xie, Tingting Zhang, Kailun Qiu, Weinan Wu, Wanyue Tan, Xiaoyi Jiang, Xiusheng Chen, Yongquan Hu, Huansen Huang, Hao Liu, Du Feng.

Mitochondria, serving as the energy hub and death-immune hub of cells, play pivotal roles in maintaining normal cellular physiology and pathological functions. Under stress conditions, mitochondria can be released from cells into the extracellular environment and even the circulatory system through multiple pathways, and subsequently taken up by other cells. The process of mitochondrial release involves complex mechanisms, exerting multifaceted effects on the fate and functions of recipient cells and playing critical roles in both physiological and pathological processes. This review focuses on the stress-induced release of mitochondria, their uptake by recipient cells, and the changes brought about in the peripheral circulation, aiming to deepen the understanding of the molecular mechanisms and biological implications of this novel mode of intercellular communication and provide new therapeutic insights for related diseases.

Keywords: circulating mitochondria; intercellular crosstalk; mitochondrial quality control; mitochondrial transfer

DOI: https://doi.org/10.1007/s11427-025-3069-3