bims-mitrat 2026-03-15 papers

bims-mitrat

Biomed News

on Mitochondrial transplantation and transfer

Issue of 2026–03–15
nine papers selected by
Gökhan Burçin Kubat, Başkent Üni̇versi̇tesi̇

Blood Flow Restriction Therapy Stimulates Intercellular Mitochondria Transfer and Improves Muscle Regeneration and Shoulder Function in a Murine Rotator Cuff Injury Model.
Mitochondria transplantation reduces intraocular pressure by improving mitochondrial function and remodeling trabecular meshwork.
Artificial mitochondria ameliorates osteoarthritis through restoring cellular energy metabolism homeostasis.
Mitochondrial transplant activates Ca2+/TFAP2A to promote hDPSCs-mediated dentin-pulp regeneration.
Revisiting the promise and pitfalls of mitochondrial replacement therapies.
Astrocytic Mitochondria Transplantation Rescues Neuron Loss and Dendritic Injuries in Acute Cerebral Ischemic Stroke Mouse Model by Flexibly Regulating Mitochondria Dynamics.
Mitochondrial transfer to granulocytic myeloid-derived suppressor cells augments immunosuppressive activity.
Structural and Functional Diversity of Mitochondria Isolated from Different Cell Types.
Cytoskeletal remodeling promotes tunneling nanotube formation and drives cardiac resident cell mitochondrial transfer in sepsis.

Am J Sports Med. 2026 Mar 08. 3635465261424875

Blood Flow Restriction Therapy Stimulates Intercellular Mitochondria Transfer and Improves Muscle Regeneration and Shoulder Function in a Murine Rotator Cuff Injury Model.

Nesa Milan, Aboubacar Wague, Luke Sang, Alex Youn, Ryan Sadjadi, Yusef Samimi, Cristhian Montenegro, Miguel Lizarraga, Justin Lau, Allan I Basbaum, Michael R Davies, Hubert T Kim, Brian T Feeley, Jarret A P Weinrich, Xuhui Liu.

   BACKGROUND: Rotator cuff (RC) tears are among the most common causes of shoulder dysfunction in sports medicine. Muscle atrophy and degeneration are important risk factors for RC tendon retearing and suboptimal recovery of shoulder function after tendon repair. Although blood flow restriction (BFR) can stimulate muscle regeneration after lower extremity trauma and anterior cruciate ligament reconstruction, the mechanisms that underlie BFR remain unknown, and its application to RC tears has not yet been explored.
HYPOTHESIS: The authors hypothesized that BFR induces transfer of mitochondria from intramuscular fibro-adipogenic progenitors (FAPs) to myocytes, enhances muscle regeneration, and improves shoulder function after RC injury.
STUDY DESIGN: Controlled laboratory study.
METHODS: To assess mitochondrial transfer after BFR, the authors used Prrx1-Cre/MitoTag reporter mice, in which FAP mitochondria are labeled. Mice underwent unilateral forelimb BFR, and supraspinatus (SS) muscles were collected at baseline and days 1, 2, 3, 5, and 7 for histology. To model massive RC tears, mice received unilateral SS and infraspinatus tendon transection with denervation (TT+DN) and then were randomized to a BFR (every 3 days) or control group. At 2 or 6 weeks after surgery, SS muscles were analyzed for mitochondrial transfer, fiber size, and fiber-type distribution. Additionally, forelimb gait and weightbearing were captured using the Blackbox system.
RESULTS: BFR was associated with increased FAP-mediated mitochondrial transfer in healthy SS muscle as early as 1 day after BFR treatment and lasted for up to 3 days after BFR. The authors observed an enhanced effect of BFR-induced FAP mitochondrial transfer in SS muscle after RC injury, compared with the control, at both 2 and 6 weeks after TT+DN. BFR-treated mice had significantly reduced muscle atrophy, fatty infiltration, and fibrosis after RC injury. They also observed a significant improvement in forepaw weightbearing ratio and ipsilateral forepaw stride length at 6 weeks after injury in BFR-treated mice compared with controls.
CONCLUSION: BFR significantly improves muscle quality and shoulder function after RC injury. These effects occur alongside increased mitochondrial transfer from FAPs to myocytes.
CLINICAL RELEVANCE: Understanding the mechanism of BFR by which BFR enhances muscle regeneration could pave the way for its use as a novel rehabilitation strategy to improve recovery in patients with RC injuries and other muscle-related conditions.

Keywords:  blood flow restriction; fibro-adipogenic progenitors; mitochondrial transfer; rotator cuff tears

DOI:  https://doi.org/10.1177/03635465261424875
J Transl Med. 2026 Mar 07. pii: 331. [Epub ahead of print]24(1):

Mitochondria transplantation reduces intraocular pressure by improving mitochondrial function and remodeling trabecular meshwork.

Xiaoling Wang, Beibei Lin, Xuegu Xu, Zhishu Bao, Ruiyi Ren, Peizhen Lin, Guangying Luo, Yongzhen Yu, Yuanbo Liang.



Keywords:  Glaucoma; Mitochondria transplantation; Mitophagy; OHT; POAG; Trabecular meshwork

DOI:  https://doi.org/10.1186/s12967-026-07964-y
Bioact Mater. 2026 Jul;61 940-966

Artificial mitochondria ameliorates osteoarthritis through restoring cellular energy metabolism homeostasis.

Wenqiang Yan, Yu Chen, Haoda Wu, Zeyuan Gao, Xiaoqing Hu, Yingfang Ao, Chun Mao, Mimi Wan.

  Mitochondrial dysfunction under pathological or aging conditions disrupts adenosine triphosphate (ATP) synthesis, exacerbating disease progression by skewing energy metabolism toward catabolism. Current strategies to restore metabolic balance remain limited by complexity or inefficiency. Inspired by the phosphocreatine-creatine kinase (CK) system-a mitochondrial-independent energy pathway, we developed chemotactic artificial mitochondria (CAMs) to address this challenge. CAMs consist of crosslinked phosphocreatine monomers (MPCr) and perfluorooctyl acrylate, designed to exploit CK's chemotactic properties for targeted delivery while resisting biofluid interference. CAMs entered degenerated chondrocytes and meniscus fibrochondrocytes via clathrin-mediated endocytosis, escaped lysosomal degradation, scavenged reactive oxygen species, and restored ATP production. Transcriptomic analysis revealed CAMs upregulated chondrogenic markers (COL2A1, ACAN, SOX9) and suppressed inflammatory pathways (MMP3, IL6), while enhancing extracellular matrix biosynthesis. In a murine knee osteoarthritis (OA) model, intra-articular CAM injections reduced synovial inflammation, preserved cartilage glycosaminoglycan content, and restored gait function by systemic metabolic reprogramming. Histological and radiographic assessments confirmed CAMs mitigated joint space narrowing and cartilage erosion. This study establishes CAMs as a robust, mitochondria-agnostic platform for treating degenerative diseases by rectifying cellular energy imbalance, with immediate translational potential for OA therapy.

Keywords:  Artificial mitochondria; Bioenergetic nanoparticles; Degenerative diseases; Energy metabolism; Osteoarthritis therapy

DOI:  https://doi.org/10.1016/j.bioactmat.2026.02.028
Stem Cell Res Ther. 2026 Mar 13.

Mitochondrial transplant activates Ca2+/TFAP2A to promote hDPSCs-mediated dentin-pulp regeneration.

Peimeng Zhan, Xinfang Zhang, Zhuo Xie, Lingling Chen, Shuheng Huang, Qiting Huang, Zhengmei Lin, Runfu Wang.

   BACKGROUND: The dentin-pulp complex (DPC) is composed of the odontoblastic layer and associated stromal components. It serves key functions in immunological homeostasis and tissue regeneration of dental tissues. Human dental pulp stem cells (hDPSCs) have emerged as pivotal cells for DPC regeneration. Current research frontiers primarily focus on developing novel strategies to increase the odontogenic differentiation potential and regenerative efficacy of hDPSCs. This study aims to boost the capacity of hDPSCs to regenerate DPC through mitochondrial transplantation.
METHODS: Mitochondria were isolated from donor hDPSCs and transplanted into recipient hDPSCs (Mito-hDPSCs) in the same passage. Subsequently, cell viability and mitochondrial transplantation efficiency were evaluated via CCK-8, β-galactosidase staining, mitochondrial imaging, and flow cytometry. Furthermore, Mito-hDPSCs' metabolic capacity was assessed by mitochondrial membrane potential assays and cellular oxidative phosphorylation assays. Moreover, Alkaline Phosphatase (ALP) activity, Alizarin Red S (ARS) staining, RT-qPCR, and Western blotting (WB) were performed to assess Mito-hDPSC's odontogenic differentiation potential. Moreover, a nude mouse model was used to assess how Mito-hDPSCs induce DPC regeneration in vivo. RNA-Seq analysis was conducted to examine the expression of signaling pathways in Mito-hDPSCs. In addition, ALP, ARS, WB, and Ca2+ fluorescence staining were carried out to analyze the underlying mechanisms between mitochondria and the Ca2+/Transcription factor activating protein 2α (TFAP2A) signaling axis.
RESULTS: The results revealed that mitochondrial transplantation enhanced the viability of Mito-hDPSCs. Furthermore, an increased mitochondrial transplant rate was observed at a recipient-to-donor cell ratio of 1:3. Moreover, Mito-hDPSCs demonstrated increased odontogenic differentiation and formed more dentin-pulp-like tissue in vivo. Ca2+ signaling and odontogenesis were significantly enriched in Mito-hDPSCs. TFAP2A was identified as a key transcription factor in the odontogenic differentiation of Mito-hDPSCs. Knockdown array revealed that mitochondrial transplantation effectively upregulated TFAP2A expression in Mito-hDPSCs. Furthermore, mitochondrial transplantation elevated intracellular Ca2+ concentration, which in turn increased TFAP2A expression.
CONCLUSIONS: Mitochondrial transplantation may promote DPC regeneration by regulating the Ca²⁺/TFAP2A signaling axis in Mito-hDPSCs.

Keywords:  Dentin-pulp complex regeneration; Human dental pulp stem cells; Mitochondrial transplantation; Odontoblast differentiation; Tissue engineering

DOI:  https://doi.org/10.1186/s13287-026-04949-y
Hum Reprod. 2026 Mar 08. pii: deag020. [Epub ahead of print]

Revisiting the promise and pitfalls of mitochondrial replacement therapies.

Nuno Costa-Borges, Dagan Wells.

  Mitochondrial replacement therapies (MRTs) have been proposed as a means of avoiding the transmission of pathogenic mitochondrial DNA (mtDNA) mutations from mother to child. While clinical cases using this groundbreaking strategy have now been reported for the two principal MRT methods-pronuclear transfer and maternal spindle transfer-recent data continues to raise questions about the reliability of these approaches for disease prevention.

Keywords:  female infertility; maternal spindle transfer; mitochondrial diseases; mitochondrial replacement therapies; mitochondrial reversal; oocyte quality; pronuclear transfer

DOI:  https://doi.org/10.1093/humrep/deag020
Ann Neurol. 2026 Mar 11.

Astrocytic Mitochondria Transplantation Rescues Neuron Loss and Dendritic Injuries in Acute Cerebral Ischemic Stroke Mouse Model by Flexibly Regulating Mitochondria Dynamics.

Ning Bian, Jianing Shen, Linwei Tian, Jinghui Li, Lu Yang, Bo Yuan, Shulin Li, Yuyu Niu, Lu Zhao, Jingkuan Wei.

OBJECTIVE: Cerebral ischemic stroke causes neuronal oxygen/energy deprivation, disrupting mitochondrial function including reduced membrane potential and bioenergetics, exacerbating neuronal injury. Mitochondrial defects are, therefore, a central neuropathological node and potential therapeutic target. Previous studies have shown that mitochondria transplantation rescued infarction in cerebral ischemic stroke. However, interactions between transplanted and endogenous mitochondria remain unclear. Here, we proposed astrocytic mitochondria as the optional donor for mitochondria transplantation in ischemic stroke treatment because of their ischemic resistance.
METHODS: We transplanted mitochondria derived from astrocytes into an ischemic stroke cell and mouse model to investigate the feasibility and mechanisms of astrocytic mitochondria transplantation for ischemic cerebral stroke. We assessed the uptake of transplanted mitochondria by neurons, their impact on endogenous mitochondrial dynamics (fusion/fission), mitochondrial functions, neuronal dendritic structure, neuronal survival, and mice motor function.
RESULTS: Transplanted astrocytic mitochondria were successfully taken up by neurons, and within neurons, they flexibly regulated endogenous mitochondrial dynamics. This intervention rescued the stroke-induced reduction in mitochondrial membrane potential and oxidative phosphorylation capacity. Consequently, it significantly decreased neuronal dendritic injuries and cell death. These cellular improvements translated into alleviated motor deficits in the stroke model.
INTERPRETATION: Astrocytic mitochondria transplantation is an effective therapeutic strategy for ischemic stroke. Its neuroprotective effects stem from the internalization of functional mitochondria into neurons and the subsequent flexibly regulation of endogenous mitochondrial dynamics, restoring bioenergetics and promoting neuronal survival. This approach holds significant promise for treating ischemic stroke and potentially other brain disorders involving mitochondrial dysfunction. ANN NEUROL 2026.

DOI: https://doi.org/10.1002/ana.78197
Cell Rep. 2026 Mar 10. pii: S2211-1247(26)00135-X. [Epub ahead of print]45(3): 117057

Mitochondrial transfer to granulocytic myeloid-derived suppressor cells augments immunosuppressive activity.

Prabhakar Arumugam, Cortney E Heim, Rachel W Fallet, Dhananjay D Shinde, Vinai C Thomas, Rafael J Argüello, Tammy Kielian.

  The anti-inflammatory properties of granulocytic myeloid-derived suppressor cells (G-MDSCs) promote Staphylococcus aureus (S. aureus) biofilm persistence. Evidence suggests that G-MDSC activity is shaped not only by S. aureus products but also by intrinsic metabolic programs. This study explores whether G-MDSC activity can be modulated by increasing mitochondrial abundance using a co-culture paradigm with macrophages as a mitochondrial donor. Macrophages transfer mitochondria directly to G-MDSCs via tunneling nanotubes, enhancing G-MDSC respiration, as reflected by increased basal, maximal, and spare respiratory capacity. Augmenting mitochondrial abundance in G-MDSCs enhances T cell-suppressive activity and reduces tumor necrosis factor (TNF) and interleukin 6 (IL-6) production. In a mouse model of S. aureus prosthetic joint infection, adoptively transferred macrophages deliver mitochondria to G-MDSCs, enhancing their suppressive activity and increasing bacterial burden, which is reversed when macrophages with non-functional mitochondria are introduced. These findings support the theory that G-MDSCs exploit mitochondria to augment their anti-inflammatory properties in response to S. aureus biofilm.

Keywords:  CP: cell biology; CP: immunology; Staphylococcus aureus; biofilm; granulocytic myeloid-derived suppressor cells; immunometabolism; macrophages; mitochondria; tunneling nanotubes

DOI:  https://doi.org/10.1016/j.celrep.2026.117057
Biol Pharm Bull. 2026 ;49(3): 457-466

Structural and Functional Diversity of Mitochondria Isolated from Different Cell Types.

Yusei Endo, Mai Kanai, Masaki Kobayashi, Yoshikazu Higami, Shoko Itakura, Makiya Nishikawa, Kosuke Kusamori.

  Mitochondria are essential organelles responsible for energy production, autophagy, and apoptosis, and mitochondrial dysfunction has been implicated in various diseases affecting the heart, liver, and kidneys. Mitochondrial transplantation, wherein isolated mitochondria are administered into cells or tissues, has recently emerged as a promising therapeutic approach for restoring cellular functions by enhancing ATP generation and reducing oxidative stress. However, the characteristics and functional diversity of the mitochondria isolated from different cell types remain poorly understood. Here, we aimed to identify the optimal mitochondrial source for transplantation therapy by comparing mitochondria isolated from several mammalian cell types, including mesenchymal stromal, hepatic, muscular, and pluripotent stem cells. Mitochondria were isolated using a streptolysin O-based isolation method and characterized through particle size, zeta potential, protein content, and ATP content. The isolated mitochondria exhibited uniform morphology, negative surface charge, sufficient protein yield, and ATP content, indicating successful preparation of functionally competent organelles suitable for comparative analysis. The mitochondria derived from mesenchymal stromal cells exhibited the highest bioenergetic activity. Adding these mitochondria enhanced cellular proliferation, oxygen consumption, and resistance to oxidative stress in recipient cells. Collectively, these findings demonstrate that mitochondria isolated from autologous mesenchymal stromal cells possess superior bioenergetic properties, highlighting their potential as an optimal source for mitochondrial transplantation therapy and providing new insights into the design of mitochondria-based therapeutics.

Keywords:  ATP production; cellular bioactivity; mesenchymal stromal cell; mitochondrial transplantation; oxidative stress

DOI:  https://doi.org/10.1248/bpb.b25-00716
Sci Adv. 2026 Mar 13. 12(11): eadz3266

Cytoskeletal remodeling promotes tunneling nanotube formation and drives cardiac resident cell mitochondrial transfer in sepsis.

Rui Song, Cheng Huang, Yinrui Ma, Zhenhua Zhang, Yifei Liu, Bing Chen, Xi Zhang, Shuai Hao, He Huang, Milad Ashrafizadeh, João Conde, Chenyang Duan.

Sepsis-induced cardiac dysfunction arises from complex intercellular communication networks that extend beyond direct cardiomyocyte damage, yet the nanoscale mechanisms governing these interactions remain poorly understood. Here, we identify tunneling nanotubes (TNTs) as dynamic biological nanostructures facilitating intercellular mitochondrial transfer, revealing their critical role in septic cardiac remodeling. Using a murine cecal ligation and puncture (CLP) model and single-cell RNA sequencing, we demonstrate that sepsis reprograms cardiac endothelial cells, fibroblasts, and macrophages, generating metabolically impaired subpopulations with dysfunctional mitochondrial respiration. We uncover a Drp1-driven cytoskeletal remodeling process that orchestrates TNT biogenesis, wherein Drp1 interacts with Filamin and Kinesin to regulate TNT formation and extension, enabling long-range organelle trafficking. Cardiac-specific Drp1 knockout disrupts TNT-mediated mitochondrial exchange, halting metabolic deterioration and reversing cellular reprogramming. These findings establish Drp1-mediated TNT networks as nanoscale conduits of organelle communication, offering insights into biological nanotube engineering, cellular-scale nanotechnology, and potential therapeutic interventions for mitochondrial dysfunction in sepsis.

DOI: https://doi.org/10.1126/sciadv.adz3266