bims-mitrat 2025-09-14 papers

Front Cell Dev Biol. 2025 ;13 1643141

The potential of mitochondrial transfer as the modifying therapy for osteoarthritis.

Yuanpei He, Xinge Wang, Boya Xu, Shichao Chen, Hongcai Li, Bei Chang, Chao Hu, Xiaorong Lan, Shiting Li, Guangwen Li.

Mitochondrial transfer is defined the process through which specific cell types release their mitochondria and subsequently transfer them to unrelated cell types in response to various physiological or pathological stimuli. This process enhances cellular function and alters disease states. Recent research has begun to explore the potential of intercellular mitochondrial transfer as a therapeutic strategy for human diseases. Mitochondrial dysfunction represents a significant pathological alteration in osteoarthritis, and studies indicate that mitochondrial transfer may serve as an effective modulatory treatment approach for osteoarthritis. Mitochondrial transfer, as an innovative subcellular therapeutic technique, presents the advantages of diverse acquisition methods and multiple transmission pathways. This paper aims to summarize the current understanding of the mechanisms of mitochondrial transfer in relation to osteoarthritis, emphasizing the existing research on mitochondrial transfer in osteoarthritis and its potential as a disease-modifying therapy.

Keywords: artificial mitochondrial transfer; disease-modifying; mitochondrial transfer; osteoarthritis; therapymitochondrial dysfunction

DOI: https://doi.org/10.3389/fcell.2025.1643141

Angiogenesis. 2025 Sep 10. 28(4): 49

Mitochondrial transfer from adipose-derived regenerative cells contributes therapeutic angiogenesis in a murine hindlimb ischemia model.

Yiyang Che, Yuuki Shimizu, Takumi Hayashi, Junya Suzuki, Zhongyue Pu, Kazuhito Tsuzuki, Shingo Narita, Yoshimitsu Yura, Rei Shibata, Toyoaki Murohara.

OBJECTIVE: Adipose-derived regenerative cells (ADRCs) are promising cell sources for damaged tissue regeneration. The efficacy of therapeutic angiogenesis with ADRC implantation in patients with critical limb ischemia has been demonstrated in clinical studies. There are several possible mechanisms in this process such as cytokines and microRNA. Recently, cell-to-cell transfer of mitochondria gains more attention in regenerative medicine. However, the role of the mitochondrial transfer mechanism in ADRCs in the regeneration of functional tissue perfusion following ischemic injury remains unclear. In this study, we aimed to investigate whether mitochondrial transfer is a potential mechanism of therapeutic angiogenesis in ADRCs using a murine hindlimb ischemia model.
METHODS AND RESULTS: In initial studies, the occurrence of mitochondrial transfer of ADRC to endothelial cells and macrophages in a series of pro-angiogenic effects of ADRC was demonstrated in a mouse model of hindlimb ischemia. Subsequently, we comprehensively elucidated the modes of mitochondrial transfer from ADRCs to HUVECs and macrophages mediated by Connexin43-based gap junctions and tunneling nanotubes using time-lapse confocal microscopy and cell sorting techniques. Furthermore, mitochondrial transfer from ADRCs enhanced mitochondrial biogenesis and angiogenesis in vascular endothelial cells and shifted macrophages toward the M2-phenotype. Notably, partially canceled mitochondrial transfer from ADRCs could impede the angiogenic ability of ADRCs in hind limb ischemia.
CONCLUSIONS: ADRCs can protect against ischemic limbs, at least in part by mitochondrial transfer via gap junctions and tunneling of nanotubes into injured endothelial cells and macrophages. Additionally, mitochondrial transfer is a potential mechanism for therapeutic angiogenesis with ADRCs in hindlimb ischemia.

Keywords: Adipose-derived regenerative cells; Angiogenesis; Hindlimb ischemia; Mitochondrial transfer

DOI: https://doi.org/10.1007/s10456-025-10001-z

Front Biosci (Landmark Ed). 2025 Aug 18. 30(8): 37006

Mitochondrial Transplantation Therapy: A Novel Approach in the Era of Organelle-Centered Regenerative Medicine.

Ha Rim Shin, Gaheon Lee, Kyung Hwa Kim.

Mitochondria play crucial roles in maintaining health and influencing disease progression by acting as central regulators of cellular homeostasis and energy production. Dysfunctions in mitochondrial activity are increasingly recognized as key contributors to various pathologies, ultimately impacting healthspan and disease outcomes. However, traditional treatments often do not restore damaged mitochondria to a healthy state. Mitochondrial transplantation, a cellular organelle-based therapy in which mitochondria are introduced into a recipient, has emerged as a novel concept in next-generation therapeutics that overcomes the limitations of current cell-based treatments. This review highlights the unique properties of mitochondria as therapeutic agents, including their ability to restore cellular functions and treat a wide range of diseases. In this review, we focus on the unique role of mitochondria in the regulation of stem cell functions, including stem cell fate, self-renewal, and differentiation. Various perspectives have been explored to better understand mitochondrial transplantation therapy, which harnesses the capacity of mitochondria as living drugs in regenerative medicine, as an innovative strategy to bridge the gap between cell therapy and organelle-based treatments and overcome current clinical barriers.

Keywords: mesenchymal stem cell; mitochondrial dysfunction; mitochondrial transplantation; organelle transplantation; regenerative medicine

DOI: https://doi.org/10.31083/FBL37006

Int J Mol Sci. 2025 Aug 27. pii: 8301. [Epub ahead of print]26(17):

Impact of Acute Myeloid Leukemia Cells on the Metabolic Function of Bone Marrow Mesenchymal Stem Cells.

Helal Ahmed, Pradeep Kumar Patnana, Yahya S Al-Matary, Maren Fiori, Jan Vorwerk, Marah H Ahmad, Eva Dazert, Lorenz Oelschläger, Axel Künstner, Bertram Opalka, Nikolas von Bubnoff, Cyrus Khandanpour.

Acute myeloid leukemia (AML) proliferation is significantly influenced by the interactions between leukemia blasts and the bone marrow (BM) microenvironment. Specifically, bone marrow mesenchymal stem cells (BMSCs) derived from AML patients (AML-MSCs) are known to support leukemia growth and facilitate disease progression. Studies have demonstrated that the transfer of mitochondria from MSCs to AML blasts not only aids in disease progression but also contributes to chemotherapy resistance. Furthermore, BM stromal cells can trigger a metabolic shift in malignant cells from mitochondrial respiration to glycolysis, which enhances both growth and chemo-resistance. This study focuses on identifying transcriptional and metabolic alterations in AML-MSCs to uncover potential targeted therapies for AML. We employed RNA sequencing and microarray analysis on MSCs cocultured with leukemic cells (MLL-AF9) and on MSCs isolated from both non-leukemic and MLL-AF9 leukemic mice. The Gene Set Enrichment Analysis (GSEA) indicated a significant downregulation of gene sets associated with oxidative phosphorylation and glycolysis in AML-MSCs. Furthermore, coculture of MSCs from wild-type mice (WT-MSCs) and a healthy donor individual (HD-MSCs) with AML cells demonstrated reduced oxidative phosphorylation and glycolysis. These metabolic changes were consistent in AML-MSCs derived from both leukemic mice and patients. Our results indicate that AML cells diminish the metabolic capacity of MSCs, specifically targeting oxidative phosphorylation and glycolysis. These findings suggest potential metabolic vulnerabilities that could be exploited to develop more effective therapeutic strategies for AML.

Keywords: acute myeloid leukemia; bone marrow mesenchymal stromal cell; metabolism

DOI: https://doi.org/10.3390/ijms26178301