Mitochondria in the Central Nervous System in Health and Disease: The Puzzle of the Therapeutic Potential of Mitochondrial Transplantation

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 410 - 410

Published: Feb. 27, 2024

Mitochondria, the energy suppliers of cells, play a central role in variety cellular processes essential for survival or leading to cell death. Consequently, mitochondrial dysfunction is implicated numerous general and CNS disorders. The clinical manifestations include metabolic disorders, immune system, tumorigenesis, neuronal behavioral abnormalities. In this review, we focus on CNS, which has unique characteristics therefore highly dependent mitochondria. First, review mitochondria development, synaptogenesis, plasticity, behavior as well their adaptation intricate connections between different types brain. Then, sparse knowledge mechanisms exogenous uptake describe attempts determine half-life transplantation long-term effects sprouting, proteome, behavior. We further discuss potential serve tool study causal link activity Next, transplantation’s therapeutic various Finally, basic reverse—translation challenges approach that currently hinder use transplantation.

Language: Английский

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Cardiotoxicity of Anticancer Drugs: Molecular Mechanisms, Clinical Management and Innovative Treatment

Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 4089 - 4116

Published: Sept. 1, 2024

With the continuous refinement of therapeutic measures, survival rate tumor patients has been improving year by year, while cardiovascular complications related to cancer therapy have become increasingly prominent. Exploring mechanism and prevention strategy therapy-related toxicity (CTR-CVT) remains one research hotspots in field Cardio-Oncology recent years. Cardiotoxicity anticancer drugs involves heart failure, myocarditis, hypertension, arrhythmias vascular toxicity, mechanistically endothelial dysfunction, ferroptosis, mitochondrial dysfunction oxidative stress. To address cardiotoxicity induced different drugs, various measures put place, such as reducing accumulation shifting with less cardiotoxicity, using cardioprotective early detection. Due very limited treatments available ameliorate drugs-induced a few innovations are being shifted from animal studies human studies. Examples include transplantation. Mitochondrial transplantation proven be effective vivo vitro experiments. Several demonstrated that intercellular transfer can doxorubicin(DOX)-induced laying foundation for innovative therapies cardiotoxicity. In this review, we will discuss current status terms pathogenesis treatment, focus on transplantation, hope review bring some inspiration you.

Language: Английский

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Bridging the gap between in vitro and in vivo models: a way forward to clinical translation of mitochondrial transplantation in acute disease states

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 31, 2024

Abstract Mitochondrial transplantation and transfer are being explored as therapeutic options in acute chronic diseases to restore cellular function injured tissues. To limit potential immune responses rejection of donor mitochondria, current clinical applications have focused on delivery autologous mitochondria. We recently convened a Transplant Convergent Working Group (CWG), explore three key issues that translation: (1) storage (2) biomaterials enhance mitochondrial uptake, (3) dynamic models mimic the complex recipient tissue environment. In this review, we present summary CWG conclusions related these provide an overview pre-clinical studies aimed at building more robust toolkit for translational trials.

Language: Английский

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INF-γ/TGF-β1-primed umbilical cord mesenchymal stem cells boost the T-lymphocytes activity: Modulation of CD25 expression and IL-6 secretion

International Journal of Immunopathology and Pharmacology, Journal Year: 2025, Volume and Issue: 39

Published: Jan. 1, 2025

Background: Mesenchymal stromal/stem cells (MSCs) have potent immunomodulatory abilities, particularly in a milieu of hyperactive immune system, through secreting number cytokines, growth factors, bioactive compounds and peptides, by cell-cell contact. During viral infection, failure immuno-neutralization the particles, recruits T-lymphocytes (T-cells) that clear virally-infected cells. MSCs greatly potentiate T-cells anti-viral activity. Objective: The objective this study is to assess ability cytokine-primed activated T-cells, towards an antiviral application. Method: Human umbilical cord (UC-MSCs) were isolated from Wharton Jelly consented donor. UC-MSCs primed with interferon (INF)-γ transforming factor (TGF)-β1. Peripheral blood using mini-max CD3+ population was purified anti-CD3 immuno-magnetic beads. Naïve or co-cultured naïve phytohemagglutinin (PHA)-activated T-cells. T-cell activation evaluated changes their rate proliferation cell count, flowcytometric immuno-phenotyping for CD25 expression, IL-6 secretion conditioned medium. Results: findings revealed count nonsignificant differed comparing five experimental groups; MSCs, T cells, coculture upon phytohemagglutinin-activation, despite reduction last two groups’ coculture. Only showed significant assessed as expression compared other groups ( p < 0.001 = 0.002, respectively). undetectable levels medium turned markedly high after cytokine-priming 0.001), reaching difference Compared secreted considerable amounts 0.001). Incubation phytohemagglutinin-activated further IL-6, level significantly higher than all aforementioned three 0.001, 0.0194, However, dampened lower observed MSCs-phytohemagglutinin-activated Conclusion: upregulated CD25+ on while hindering without affecting rate. This may point potentially stronger effects, alleviating infection-induced cytokine storm.

Language: Английский

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Silicon Enhances Functional Mitochondrial Transfer to Improve Neurovascularization in Diabetic Bone Regeneration

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Abstract Diabetes mellitus is a metabolic disorder associated with an increased risk of fractures and delayed fracture healing, leading to higher prevalence bone defects. Recent advancements in strategies aim at regulating immune responses enhancing neurovascularization have not met expectations. This study demonstrates that silicon‐based strategy significantly enhances vascularization innervation, thereby optimizing the repair diabetic Silicon improves mitochondrial function modulates fission dynamics macrophages via Drp1‐Mff signaling pathway. Subsequently, functional mitochondria are transferred from endothelial neuronal cells through microvesicles, providing protective mechanism for blood vessels peripheral nerves during early wound healing. On this basis, optimized combining silicified collagen scaffold Drp1‐Fis1 interaction inhibitor used further regulate enhance trafficking into stressed receptor cells. In mice critical‐sized calvarial defects, treatment promotes vessel formation, nerve growth, mineralized tissue development. These findings provide therapeutic insights role silicon promoting regeneration highlight importance intercellular communication conditions.

Language: Английский

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Gastric Cancer Actively Remodels Mechanical Microenvironment to Promote Chemotherapy Resistance via MSCs‐Mediated Mitochondrial Transfer

Advanced Science, Journal Year: 2024, Volume and Issue: 11(47)

Published: Oct. 11, 2024

Chemotherapy resistance is the main reason of treatment failure in gastric cancer (GC). However, mechanism oxaliplatin (OXA) remains unclear. Here, we demonstrate that extracellular mechanical signaling plays crucial roles OXA within GC. We selected OXA-resistant GC patients and analyzed tumor tissues by single-cell sequencing, found mitochondrial content cells increased a biosynthesis-independent manner. Moreover, mitochondria were mainly derived from mesenchymal stromal (MSCs), which could repair function reduce levels mitophagy cells, thus leading to resistance. Furthermore, investigated underlying transfer was mediated signals matrix (ECM). After administration, actively secreted ECM microenvironment (TEM), increasing stiffness tissues, promoted MSCs via microvesicles (MVs). Meanwhile, inhibiting mechanical-related RhoA/ROCK1 pathway alleviate cells. In summary, these results indicate be used as an indicator identify chemotherapy resistance, targeting effectively improve therapeutic efficacy.

Language: Английский

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Special Issue “Mesenchymal Stromal Cells’ Involvement in Human Diseases and Their Treatment”

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1269 - 1269

Published: Jan. 20, 2024

Mesenchymal stromal cells (MSCs) are multipotent, non-hematopoietic that have the ability to differentiate into several mature cell types, including adipocytes, chondrocytes, osteoblasts, and myoblasts [...].

Language: Английский

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Astragalus polysaccharides augment BMSC homing via SDF-1/CXCR4 modulation: a novel approach to counteract peritoneal mesenchymal transformation and fibrosis

BMC Complementary Medicine and Therapies, Journal Year: 2024, Volume and Issue: 24(1)

Published: May 24, 2024

Abstract Purpose This study aimed to evaluate the potential of astragalus polysaccharide (APS) pretreatment in enhancing homing and anti-peritoneal fibrosis capabilities bone marrow mesenchymal stromal cells (BMSCs) elucidate underlying mechanisms. Methods Forty male Sprague-Dawley rats were allocated into four groups: control, peritoneal dialysis fluid (PDF), PDF + BMSCs, APS BMSCs (APS-pre-treated BMSCs). A model was induced using PDF. Dil-labeled administered intravenously. Post-transplantation, BMSC peritoneum pathological alterations assessed. Stromal cell-derived factor-1 (SDF-1) levels quantified via enzyme-linked immunosorbent assay (ELISA), while CXCR4 expression determined PCR immunofluorescence. Additionally, a co-culture system involving mesothelial (PMCs) established Transwell setup examine vitro effects on migration therapeutic efficacy, with inhibitor AMD3100 deployed dissect role SDF-1/CXCR4 axis its downstream impacts. Results In vivo experiments confirmed that pre-treatment notably facilitated targeted tissue PDF-treated rats, thereby amplifying their impact. exposure markedly increased SDF-1 serum samples, which encouraged CXCR4-positive BMSCs. Inhibition through application diminished migration, consequently attenuating response mesenchyme-to-mesothelial transition (MMT). Furthermore, upregulated intensified activation axis’s pathways, partially reversed AMD3100-induced effects. Conclusion augments pathway by increasing action bolsters amplifies suppressive influence MMT, improving fibrosis.

Language: Английский

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Integrating Mitochondrial Biology into Innovative Cell Therapies for Neurodegenerative Diseases

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(9), P. 899 - 899

Published: Sept. 5, 2024

The role of mitochondria in neurodegenerative diseases is crucial, and recent developments have highlighted its significance cell therapy. Mitochondrial dysfunction has been implicated various disorders, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, Huntington's diseases. Understanding the impact mitochondrial biology on these conditions can provide valuable insights for developing targeted therapies. This mini-review refocuses emphasizes potential therapies leveraging mesenchymal stem cells, embryonic induced pluripotent cell-derived secretions, extracellular vesicles. Mesenchymal cell-mediated transfer restoring health cells with dysfunctional mitochondria. Additionally, attention paid to gene-editing techniques such as mito-CRISPR, mitoTALENs, mito-ZNFs, DdCBEs ensure safety efficacy treatments. Challenges future directions are also discussed, possible tumorigenic effects off-target effects, disease targeting, immune rejection, ethical issues.

Language: Английский

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Imbalance of early-life vitamin D intake targets ROS-mediated crosstalk between mitochondrial dysfunction and differentiation potential of MSCs associated the later obesity

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 13, 2024

Obesity is characterized by excessive fat accumulation, which related with abnormal pluripotency of mesenchymal stem cells (MSCs). Recently, there growing evidence that the disorder maternal vitamin D (VD) intake a well-known risk factor for long-term adverse health outcomes to their offspring. Otherwise, less known its repercussion and underlying mechanisms on different differentiation potential MSCs. Four-week-old female C57BL/6J mice were fed VD reproductive diets throughout whole pregnancy lactation. The characteristics BMSCs from seven-day male offspring, VDR knockdown establishment HuMSCs under interventions in vitro confirmed flow cytometry, RT-PCR, immunofluorescence. roles mitochondrial dysfunction also investigated. Then remaining weaned pups induced administrating high-fat-diet (HFD) 16 weeks normal diet was simultaneously as controls. Their lipid accumulation adipocytes hypertrophy determined histological staining gene expressions. Herein, it proved imbalance early-life could significantly aggravate occurrence obesity inducing adipogenesis through affecting metabolism metabolites (P < 0.05). Moreover, abnormally might be involved disorders inhibit maintenance MSCs stemness increasing productions ROS, accompanied impairing expression genes adipo-osteogenic along adipogenic higher ROS state deficiency, while status conversely enhance osteogenic slightly lower Furthermore, mitochondria dysfunctional, especially mitophagy, activating LC3b, P62 etc. using vivo studies These findings demonstrated target ROS-mediated crosstalk between MSCs, associated later obesity. Obviously, our results open up an attractive modality benefits suitable during

Language: Английский

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