bims-mitrat 2025-03-09 papers

bims-mitrat

Biomed News

on Mitochondrial transplantation and transfer

Issue of 2025–03–09
seven papers selected by
Gökhan Burçin Kubat, Gulhane Health Sciences Institute

Enhancing radiation-induced reactive oxygen species generation through mitochondrial transplantation in human glioblastoma.
Dental pulp stem cells alleviate Schwann cell pyroptosis via mitochondrial transfer to enhance facial nerve regeneration.
Connecting the dots: Mitochondrial transfer in immunity, inflammation, and cancer.
Engineered mitochondria in diseases: mechanisms, strategies, and applications.
Mitochondria in aging and age-associated diseases.
Human umbilical cord-derived mesenchymal stem cells attenuate liver fibrosis by inhibiting hepatocyte ferroptosis through mitochondrial transfer.
Development of a Microfluidic System for Mitochondrial Extraction, Purification, and Analysis.

Sci Rep. 2025 Mar 04. 15(1): 7618

Enhancing radiation-induced reactive oxygen species generation through mitochondrial transplantation in human glioblastoma.

Kent L Marshall, Murugesan Velayutham, Valery V Khramtsov, Alan Mizener, Christopher P Cifarelli.

  Glioblastoma (GBM) is the most aggressive primary brain malignancy in adults, with high recurrence rates and resistance to standard therapies. This study explores mitochondrial transplantation as a novel method to enhance the radiobiological effect (RBE) of ionizing radiation (IR) by increasing mitochondrial density in GBM cells, potentially boosting reactive oxygen species (ROS) production and promoting radiation-induced cell death. Using cell-penetrating peptides (CPPs), mitochondria were transplanted into GBM cell lines U3035 and U3046. Transplanted mitochondria were successfully incorporated into recipient cells, increasing mitochondrial density significantly. Mitochondrial chimeric cells demonstrated enhanced ROS generation post-irradiation, as evidenced by increased electron paramagnetic resonance (EPR) signal intensity and fluorescent ROS assays. The transplanted mitochondria retained functionality and viability for up to 14 days, with mitochondrial DNA (mtDNA) sequencing confirming high transfection and retention rates. Notably, mitochondrial transplantation was feasible in radiation-resistant GBM cells, suggesting potential clinical applicability. These findings support mitochondrial transplantation as a promising strategy to overcome therapeutic resistance in GBM by amplifying ROS-mediated cytotoxicity, warranting further investigation into its efficacy and mechanisms in vivo.

Keywords:  Cell-penetrating peptide; EPR; Glioblastoma; Mitochondria; RBE; ROS; Radiation

DOI:  https://doi.org/10.1038/s41598-025-91331-2
Bioact Mater. 2025 May;47 313-326

Dental pulp stem cells alleviate Schwann cell pyroptosis via mitochondrial transfer to enhance facial nerve regeneration.

Xiaoyu Zheng, Juan Wang, Heng Zhou, Ying Chai, Ziwei Li, Minjie Chen, Zihan Yang, Chun Xu, Chang Lei, Yan He, Duohong Zou, Qingsong Ye.

  Dental pulp stem cells (DPSCs) have demonstrated remarkable potential in enhancing peripheral nerve regeneration, though the precise mechanisms remain largely unknown. This study investigates how DPSCs alleviate Schwann cell pyroptosis and restore mitochondrial homeostasis through intercellular mitochondrial transfer. In a crab-eating macaque model, we first observed that DPSC-loaded nerve conduits significantly promoted long-term nerve regeneration, facilitating tissue proliferation and myelin recovery. We further established a rat facial nerve injury (FNI) model and found that DPSC treatment reduced pyroptosis and mitochondrial ROS production in Schwann cells. A pivotal mitochondrial protective mechanism, resembling the effects of a ROS-targeted inhibitor, involved the transfer of mitochondria from DPSCs to pyroptosis-induced Schwann cells via tunneling nanotubes, while blocking intercellular junctions or mitochondrial function diminished the therapeutic effects. TNFα secreted by pyroptosis-induced Schwann cells activated the NF-κB pathway in DPSCs, enhancing mitochondrial transfer and adaptive stress responses, thereby promoting mitochondrial protection against pyroptosis in Schwann cells, as reflected in the improved therapeutic efficacy of TNFα-preconditioned DPSCs in the FNI model. These findings unveil a mechanism through which DPSCs foster nerve regeneration via mitochondrial transfer, presenting a promising strategy for enhancing stem cell-based therapies for nerve injuries.

Keywords:  Dental pulp stem cells; Facial nerve regeneration; Mitochondrial transfer

DOI:  https://doi.org/10.1016/j.bioactmat.2025.01.031
Immunol Lett. 2025 Mar 06. pii: S0165-2478(25)00024-0. [Epub ahead of print]274 106992

Connecting the dots: Mitochondrial transfer in immunity, inflammation, and cancer.

Valentina Artusa, Lara De Luca, Mario Clerici, Daria Trabattoni.

  Mitochondria are more than mere energy generators; they are multifaceted organelles that integrate metabolic, signalling, and immune functions, making them indispensable players in maintaining cellular and systemic health. Mitochondrial transfer has recently garnered attention due to its potential role in several physiological and pathological processes. This process involves multiple mechanisms by which mitochondria, along with mitochondrial DNA and other components, are exchanged between cells. In this review, we examine the critical roles of mitochondrial transfer in health and disease, focusing on its impact on immune cell function, the resolution of inflammation, tissue repair, and regeneration. Additionally, we explore its implications in viral infections and cancer progression. We also provide insights into emerging therapeutic applications, emphasizing its potential to address unmet clinical needs.

Keywords:  Cancer; Immunity; Inflammation; Mitochondrial transfer; Mitotherapy

DOI:  https://doi.org/10.1016/j.imlet.2025.106992
Signal Transduct Target Ther. 2025 Mar 03. 10(1): 71

Engineered mitochondria in diseases: mechanisms, strategies, and applications.

Mingyang Li, Limin Wu, Haibo Si, Yuangang Wu, Yuan Liu, Yi Zeng, Bin Shen.

Mitochondrial diseases represent one of the most prevalent and debilitating categories of hereditary disorders, characterized by significant genetic, biological, and clinical heterogeneity, which has driven the development of the field of engineered mitochondria. With the growing recognition of the pathogenic role of damaged mitochondria in aging, oxidative disorders, inflammatory diseases, and cancer, the application of engineered mitochondria has expanded to those non-hereditary contexts (sometimes referred to as mitochondria-related diseases). Due to their unique non-eukaryotic origins and endosymbiotic relationship, mitochondria are considered highly suitable for gene editing and intercellular transplantation, and remarkable progress has been achieved in two promising therapeutic strategies-mitochondrial gene editing and artificial mitochondrial transfer (collectively referred to as engineered mitochondria in this review) over the past two decades. Here, we provide a comprehensive review of the mechanisms and recent advancements in the development of engineered mitochondria for therapeutic applications, alongside a concise summary of potential clinical implications and supporting evidence from preclinical and clinical studies. Additionally, an emerging and potentially feasible approach involves ex vivo mitochondrial editing, followed by selection and transplantation, which holds the potential to overcome limitations such as reduced in vivo operability and the introduction of allogeneic mitochondrial heterogeneity, thereby broadening the applicability of engineered mitochondria.

DOI: https://doi.org/10.1038/s41392-024-02081-y
Mitochondrion. 2025 Feb 27. pii: S1567-7249(25)00019-4. [Epub ahead of print]82 102022

Mitochondria in aging and age-associated diseases.

Sonu Pahal, Nirjal Mainali, Meenakshisundaram Balasubramaniam, Robert J Shmookler Reis, Srinivas Ayyadevara.

Mitochondria, essential for cellular energy, are crucial in neurodegenerative disorders (NDDs) and their age-related progression. This review highlights mitochondrial dynamics, mitovesicles, homeostasis, and organelle communication. We examine mitochondrial impacts from aging and NDDs, focusing on protein aggregation and dysfunction. Prospective therapeutic approaches include enhancing mitophagy, improving respiratory chain function, maintaining calcium and lipid balance, using microRNAs, and mitochondrial transfer to protect function. These strategies underscore the crucial role of mitochondrial health in neuronal survival and cognitive functions, offering new therapeutic opportunities.

DOI: https://doi.org/10.1016/j.mito.2025.102022
Free Radic Biol Med. 2025 Feb 27. pii: S0891-5849(25)00128-5. [Epub ahead of print]231 163-177

Human umbilical cord-derived mesenchymal stem cells attenuate liver fibrosis by inhibiting hepatocyte ferroptosis through mitochondrial transfer.

Zhiyu Xiong, Ping Chen, Zheng Wang, Lichao Yao, Mengqin Yuan, Pingji Liu, Muhua Sun, Kan Shu, Yingan Jiang.

  Liver fibrosis is a reversible dynamic pathological process induced by chronic liver injury. Without intervention, liver fibrosis can progress to become cirrhosis, liver failure, or hepatocellular carcinoma, thus posing a high global health burden. Therefore, effective therapies for liver fibrosis are urgently required. Although transplantation of mesenchymal stem cells (MSCs) has significant value as a treatment strategy for liver damage, the underlying mechanisms remain unclear. Chronic liver injury progression is significantly influenced by hepatocyte ferroptosis, and targeting ferroptosis is emerging as a potential treatment strategy for liver fibrosis. Here, we showed that the infusion of human umbilical cord-derived MSCs (hUC-MSCs) alleviated TAA-induced liver fibrosis, improved liver functionality, and decreased ferroptosis in mice. hUC-MSCs inhibit ferroptosis-related mitochondrial damage and lipid peroxidation in AML12 cells in vitro. Mechanistically, under oxidative stress, hUC-MSCs transfer healthy mitochondria to damaged hepatocytes through tunneling nanotubes (TNTs). Cytochalasin D (CytoD), an inhibitor of TNT formation, abrogated the protective effects of hUC-MSCs against ferroptosis. This research emphasizes the ability of hUC-MSCs to serve as a promising treatment for liver fibrosis via mitochondrial transfer through TNTs.

Keywords:  Ferroptosis; Liver fibrosis; Mitochondria transfer; TNTs; hUC-MSCs

DOI:  https://doi.org/10.1016/j.freeradbiomed.2025.02.045
ACS Appl Mater Interfaces. 2025 Mar 04.

Development of a Microfluidic System for Mitochondrial Extraction, Purification, and Analysis.

Rukhsar Ajmal, Weisen Zhang, Hui Liu, Hua Bai, Lei Cao, Bo Peng, Lin Li.

  Mitochondria, as essential cellular organelles, play a key role in numerous diseases, from neurodegenerative disorders to cancer and rare conditions. The extraction of mitochondria from cells has many applications in disease diagnosis, pathological research, and emerging mitochondrial transplantation therapy (MTT). Recent advancements in microfluidic-on-chip systems offer promising improvements in mitochondrial extraction by enabling high-throughput processing, precise control, and flexibility while facilitating integration with other devices and platforms. Despite growing interest in microfluidic mitochondrial extraction (MME), there is a lack of comprehensive reviews on the latest developments in this field. This review aims to summarize recent advancements as well as the advantages and limitations of MME, providing deeper insights into microfluidic-based approaches for mitochondrial extraction, purification, and analysis.

Keywords:  Microfluidic Mitochondrial Extraction; Microfluidic-based Separation; Microfluidics; Mitochondria; Mitochondrial Transplantation Therapy

DOI:  https://doi.org/10.1021/acsami.4c18415