bims-mitrat 2025-06-01 papers

Cell Tissue Res. 2025 May 26.

Tissue-specific differences impacts therapeutic outcomes of mitochondrial transplantation through regulation of bioenergetics in metabolic syndrome.

Jyotsna Pareek, Pallavi Mudgal, Nitika Sindhu, Vaibhav Tiwari, Dinesh Mani Tripathi, Swati Paliwal.

Mitochondria transplantation is an emerging therapeutic strategy with remarkable potential in treating various diseases associated with mitochondrial dysfunction. Despite the known differences in tissue-specific mitochondria, the therapeutic outcomes of mitochondria isolated from various sources, after their transplantation in a specific disease model has remained elusive. In this study, we investigated the tissue-dependent therapeutic differences after transplantation of mitochondria isolated from heart, muscle, and liver tissues in a high-fat diet and streptozotocin, 35 mg/Kg (HFD + STZ) induced metabolic syndrome (MetS) in Wistar rats. We found striking differences in lowering of blood glucose levels, blood pressure, cholesterol, ALT, and AST levels in MetS after transplantation of mitochondria obtained from heart, muscle, and liver tissues (P < 0.01). Liver mitochondria transplantation demonstrated the most effective upregulation of mitochondrial complex activities, enhanced anti-oxidant enzyme levels in recipient liver tissues (P < 0.01). It also upregulated gene expression of genes associated with mitochondrial biogenesis and bioenergetics and reduced apoptosis and inflammation associated genes in HFD + STZ rats. In addition, GC-MS metabolite analysis revealed differential blood serum concentrations of key tri-carboxylic acid metabolites such as succinic acid, malic acid, alpha-ketoglutarate, citric acid, and pyruvate after mitochondrial transplantation in HFD + STZ rats. This study supports the idea that mitochondria source tissue should be considered to provide better clinical outcomes for mitochondrial transplantation.

Keywords: Metabolic syndrome; Mitochondrial transplantation; Therapeutic potential; Tissue source

DOI: https://doi.org/10.1007/s00441-025-03977-z

Tissue Cell. 2025 May 24. pii: S0040-8166(25)00270-8. [Epub ahead of print]96 102990

Mitochondria transfer from mesenchymal stem cells into osteoarthritic chondrocytes ameliorate cellular functions and alleviate both inflammation and oxidative stress.

Candan Altuntaş, Gökhan Duruksu, Fatih Hunç, Yusufhan Yazir.

OBJECTIVE: Osteoarthritis, a common age-related joint disease, causes cartilage degeneration, leading to pain and disability. While pain management exists, cartilage regeneration options are limited. Exogenous mitochondria transfer is a novel regenerative approach. This study aimed to investigate the effects of exogenous mitochondrial transfer on cellular function, oxidative stress, inflammation, and apoptosis in osteoarthritic chondrocytes.
METHODS: Two inflammatory models using M1-macrophage conditioned medium or co-culture with synovial fluid mesenchymal stem cells (MSCs) were established. The study compared mitochondria from Wharton's jelly (WJ-) and bone marrow (BM-) MSCs by analyzing their transfer to these models. Transfer effects were evaluated by mitochondrial membrane potential, cell viability, apoptosis, gene expression, and oxidative state.
RESULTS: Mitochondria tracking showed high transfer efficiencies (99.62 % for WJ-MSCs, 91.34 % for BM-MSCs). Late apoptosis was significantly reduced after transfer of WJ-MSCs mitochondria from 5.58 % to 2.93 % in the model with M1-macrophage conditioned medium. Expression of TNF-α and IL-1β was reduced after mitochondrial delivery. The expression of Ki67 was induced in parallel with increased ATP production and reduced HMOX-1 expression levels after the transfer. A decrease of 2.5- and 5-fold in ATP levels in cells after the inflammatory models were recovered after WJ-MSCs mitochondria transfer by 3.1- and 100-fold depending on the inflammatory model used. Although ROS levels remained unchanged, MDA levels decreased, and collagen type-2 expression increased.
CONCLUSION: Mitochondria transfer improved key aspects of chondrocyte dysfunction in inflammatory osteoarthritis models. These findings support its therapeutic potential for treating or slowing osteoarthritis by directly improving damaged chondrocyte health and function.

Keywords: Chondrogenic differentiation; Macrophages; Mesenchymal stem cells; Mitochondria transfer; Osteoarthritis

DOI: https://doi.org/10.1016/j.tice.2025.102990

BMC Neurol. 2025 May 27. 25(1): 227

Mitotherapy in Alzheimer's and Parkinson's diseases: A systematic review of preclinical studies.

Aynur Modiri, Leila Hosseini, Nasrin Abolhasanpour, Hosein Azizi, Reza Naghdi Sadeh.

BACKGROUND: Alzheimer's disease (AD) and Parkinson's disease (PD) are prevalent neurodegenerative disorders and strongly affect both the patients' lives and their caregivers. Strategy to improve and restore mitochondrial function, as well as to treat mitochondria-associated diseases, as observed in the pathophysiology of AD and PD. The current study aimed to investigate the potential of mitotherapy in AD and PD in preclinical studies.
METHODS: We conducted a systematic search of articles in English related to mitotherapy in AD and PD animal models published until October 2024 in the selected bibliographic databases, including PubMed, Scopus, EMBASE, and Google Scholar, and the reference lists of relevant review articles published. The quality of the final selected studies was assessed using the Collaborative Approach to Meta-Analysis and Review of Animal Studies (CAMARADES) checklists and the SYRCLE risk of bias tool. The initial search resulted in 231 studies, and after screening the titles and abstracts, 30 studies were recognized. Finally, 7 studies met the inclusion criteria.
RESULTS: Despite restricted knowledge of the mitotherapy mechanisms, evidence shows that exogenous mitochondria exert neuroprotective effects via improving mitochondrial function, reducing oxidative stress and inflammation in preclinical models of AD and PD.
CONCLUSION: This systematic review summarizes the preclinical studies on mitotherapy and provides evidence favoring mitochondria transplantation's protective effects in animal PD and AD models.

Keywords: Alzheimer's disease; Mitochondrial dysfunction; Mitochondrial transfer; Parkinson's disease

DOI: https://doi.org/10.1186/s12883-025-04241-1

J Nanobiotechnology. 2025 May 28. 23(1): 389

Extracellular vesicles from adipose-derived stromal/stem cells reprogram dendritic cells to alleviate rat TMJOA by transferring mitochondria.

Ziyi Mei, Hanyue Li, Chuling Huang, Shiyong Ma, Yuejia Li, Pingmeng Deng, Sha Zhou, Aizhuo Qian, Bin Yang, Jie Li.

Temporomandibular joint osteoarthritis (TMJOA) urgently needs regenerative therapies due to the limited effects of traditional treatments. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are considered a potent alternative for MSC therapy for the treatment of TMJOA. However, the specific mechanisms remain inadequately investigated. In this study, we explored how EVs from adipose-derived stromal/stem cells (ASCs) influence the TMJOA model triggered by Complete Freund's Adjuvant in rats and their impact on the state of dendritic cells (DCs) under pathological conditions. Subsequently, we conducted transcriptomic and metabolomic analyses to elucidate the specific mechanisms by which EVs affect DCs. Mechanistically, we demonstrate that EVs transferred functional mitochondria to DCs, which reverses their metabolic states. The internalized functional mitochondria from EVs activate the MAPK/ERK1/2/FoxO1/autophagy pathway, which causes the metabolic reprogramming of DCs and facilitates the achievement of therapeutic effects. These findings provide a mechanistic rationale for utilizing ASCs-EVs as cell-free alternatives to MSC transplantation in TMJOA therapy.

Keywords: Autophagy; Dendritic cells; Extracellular vesicles; Mitochondria; Reprogramming metabolism

DOI: https://doi.org/10.1186/s12951-025-03478-9