Extracellular vesicles in kidney disease

Nature Reviews Nephrology, Journal Year: 2022, Volume and Issue: 18(8), P. 499 - 513

Published: May 31, 2022

Language: Английский

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Adverse events, side effects and complications in mesenchymal stromal cell-based therapies

Stem Cell Investigation, Journal Year: 2022, Volume and Issue: 9, P. 7 - 7

Published: Nov. 1, 2022

Abstract: Numerous clinical studies have shown a wide potential of mesenchymal stromal cells (MSCs) application. However, recent experience has accumulated numerous reports adverse events and side effects associated with MSCs therapy. Furthermore, the strategies methods therapy did not change significantly in decades despite impact awareness complications. An extended understanding limitations could lead to wider implementation safe cell therapies avoid harmful approaches. Therefore, our objective was summarize possible negative observed during MSCs-based therapies. We were also aimed discuss risks caused by weaknesses processing, including isolation, culturing, storage. Cell processing culture dramatically influence population profile, protein expression differentiation paving way for future effects. Long-term led accumulation chromosomal abnormalities. Overdosed antibiotics media enhanced risk mycoplasma contamination. Clinical trials reported thromboembolism fibrosis as most common Their delayed manifestation generally depends on patient's individual phenotype requires specific obligatory inclusion patient' informed consents. Finally we prepared safety checklist, recommended specialists before administration or planning

Language: Английский

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Mesenchymal stem cell-derived exosomes protect against liver fibrosis via delivering miR-148a to target KLF6/STAT3 pathway in macrophages

Stem Cell Research & Therapy, Journal Year: 2022, Volume and Issue: 13(1)

Published: July 20, 2022

Abstract Background Despite emerging evidence on the therapeutic potential of mesenchymal stem cells (MSCs) for liver fibrosis, underlying mechanisms remain unclear. At present, MSC-derived exosomes (MSC-EXOs) are widely accepted as crucial messengers intercellular communication. This study aimed to explore effects MSC-EXOs fibrosis and identify action MSC-EXOs. Methods Carbon tetrachloride was used induce a model, which intravenously administered with MSCs or assess treatment efficacy. The resulting histopathology, degree, inflammation macrophage polarization were analyzed. RAW264.7 BMDM regulatory polarization. Then, critical miRNA mediating screened via RNA sequencing validated experimentally. Furthermore, target mRNA downstream signaling pathways elucidated by luciferase reporter assay, bioinformatics analysis western blot. Results alleviated largely depended their secreted exosomes, visualized circulate into after transplantation. In addition, found modulate phenotype regulate inflammatory microenvironment in repair injury. Mechanically, RNA-sequencing illustrates that miR-148a, enriched MSC-EXOs, targets Kruppel-like factor 6 (KLF6) suppress pro-inflammatory macrophages promote anti-inflammatory inhibiting STAT3 pathway. Administration miR-148a-enriched miR-148a agomir shows potent ameliorative fibrosis. Conclusions These findings suggest protect against delivering regulates intrahepatic functions through KLF6/STAT3 provide

Language: Английский

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Extracellular Vesicle Heterogeneity and Its Impact for Regenerative Medicine Applications

Pharmacological Reviews, Journal Year: 2023, Volume and Issue: 75(5), P. 1043 - 1061

Published: June 6, 2023

Extracellular vesicles (EVs) are cell-derived membrane enclosed particles that involved in physiological and pathological processes. EVs increasingly being studied for therapeutic applications the field of regenerative medicine. Therapeutic application stem has shown great potential to stimulate tissue repair. However, exact mechanisms through which they induce this effect not been fully clarified. This may a large extent be attributed lack knowledge on EV heterogeneity. Recent studies suggest represent heterogeneous population with distinct functions. The heterogeneity can differences their biogenesis, as such, classified into populations then further subcategorized various subpopulations. A better understanding is crucial elucidating action regeneration. review provides an overview latest insights related repair, including different characteristics contribute such heterogeneity, well functional among subtypes. It also sheds light challenges hinder clinical translation EVs. Additionally, innovative isolation techniques studying discussed. Improved active subtypes would promote development tailored therapies aid researchers EV-based therapeutics clinic. Significance Statement Within we discuss properties subpopulations, implications therapeutics. We aim provide new aspects leading preparations, stress importance applications.

Language: Английский

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Recent advances to enhance the immunomodulatory potential of mesenchymal stem cells

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 23, 2022

Considering the unique therapeutic potential of mesenchymal stem cells (MSCs), including their immunosuppressive and immunomodulatory properties as well ability to improve tissue regeneration, these have attracted attention scientists clinicians for treatment different inflammatory immune system mediated disorders. However, various clinical trials using MSCs purpose are conflicting differ from results promising preclinical studies. This inconsistency is caused by several factors such poor migration homing capacities, low survival rate, level proliferation differentiation, donor-dependent variation cells. Enhancement retention persistent effects remain a challenge overcome in MSC-based therapy. In this review, we summarized approaches enhance outcomes therapy revised current future perspectives creation cellular products with improved diverse applications.

Language: Английский

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Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles

World Journal of Stem Cells, Journal Year: 2022, Volume and Issue: 14(7), P. 453 - 472

Published: July 26, 2022

The use of mesenchymal stem-cells (MSC) in cell therapy has received considerable attention because their properties. These properties include high expansion and differentiation vitro, low immunogenicity, modulation biological processes, such as inflammation, angiogenesis hematopoiesis. Curiously, the regenerative effect MSC is partly due to paracrine activity. This prompted numerous studies, investigate therapeutic potential secretome general, specifically extracellular vesicles (EV). latter contain proteins, lipids, nucleic acids, other metabolites, which can cause physiological changes when released into recipient cells. Interestingly, contents EV be modulated by preconditioning under different culture conditions. Among them, exposure hypoxia stands out; these cells respond activating hypoxia-inducible factor (HIF) at O2 concentrations. HIF direct indirect pleiotropic effects, modulating expression hundreds genes involved processes migration, proliferation, differentiation, angiogenesis, metabolism, apoptosis. Expression reflected secreted EV. studies show that MSC-derived conditioned have a higher capacity than those obtained normoxia. In this review, we implications responses relation tissue regeneration. addition, being evaluated very attractive strategy for isolation EV, with clinical medicine applied pathologies.

Language: Английский

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Hypoxia endothelial cells-derived exosomes facilitate diabetic wound healing through improving endothelial cell function and promoting M2 macrophages polarization

Bioactive Materials, Journal Year: 2023, Volume and Issue: 33, P. 157 - 173

Published: Nov. 10, 2023

It is imperative to develop and implement newer, more effective strategies address refractory diabetic wounds. As of now, there currently no optimal solution for these Hypoxic human umbilical vein endothelial cells (HUVECs)-derived exosomes have been postulated promote wound healing, however, its effect molecular mechanism need further study. In this study, we aimed investigate whether hypoxic enhance healing in diabetics. Based on our high-throughput sequencing, differentially expressed lncRNAs (including 64 upregulated 94 downregulated lncRNAs) were found compared normoxic exosomes. Interestingly, lncHAR1B was one the prominently exosomes, showing a notable correlation with healing. More specifically, transmitted surrounding cells, which resulted significant increase level, thereby relieving dysfunction promoting switch from M1 M2 macrophages under high glucose conditions. Mechanistically, directly interacted transcription factor basic helix-loop-helix family member e23 (BHLHE23), subsequently led binding KLF 4 (KLF4) promoted KLF4 expression.

Language: Английский

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MSC-EVs alleviate osteoarthritis by regulating microenvironmental cells in the articular cavity and maintaining cartilage matrix homeostasis

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 85, P. 101864 - 101864

Published: Jan. 25, 2023

Language: Английский

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Mesenchymal Stem Cell Senescence during Aging:From Mechanisms to Rejuvenation Strategies

Aging and Disease, Journal Year: 2023, Volume and Issue: 14(5), P. 1651 - 1651

Published: Jan. 1, 2023

In cell transplantation therapy, mesenchymal stem cells(MSCs)are ideal seed cells due to their easy acquisition and cultivation, strong regenerative capacity, multi-directional differentiation abilities, immunomodulatory effects. Autologous MSCs are better applicable compared with allogeneic in clinical practice. The elderly the main population for but as donor aging, tissue show aging-related changes. When number of generations vitro expansion is increased, will also exhibit replicative senescence. quantity quality decline during which limits efficacy autologous therapy. this review, we examine changes MSC senescence a result discuss progress research on mechanisms signalling pathways senescence, possible rejuvenation strategies aged combat enhance health therapeutic potential MSCs.

Language: Английский

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Hypoxia‐Preconditioned BMSC‐Derived Exosomes Induce Mitophagy via the BNIP3–ANAX2 Axis to Alleviate Intervertebral Disc Degeneration

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: July 8, 2024

Intervertebral disc degeneration (IVDD) is a chronic degenerative disease involving the aging and loss of proliferative capacity nucleus pulposus cells (NPCs), processes heavily dependent on mitochondrial dynamics autophagic flux. This study finds that absence BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) associated with senescence-related NPC degeneration, disrupting quality control. Bone marrow mesenchymal stem (BMSCs) have multidirectional differentiation potential produce extracellular vesicles containing cellular activators. Therefore, in this study, BMSCs are induced under hypoxic stimulation to deliver BNIP3-rich NPCs, thereby alleviating aging-associated flux, promoting damaged clearance, restoring Mechanistically, BNIP3 shown interact membrane-bound annexin A2 (ANXA2), enabling liberation transcription factor EB (TFEB) from ANXA2-TFEB complex, TFEB nuclear translocation, regulating autophagy lysosomal gene activation. Furthermore, rat model IVDD established verified vivo efficacy exosomes repairing injuries, delaying aging, matrix (ECM) synthesis. In summary, hypoxia-induced BMSC alleviate by activating BNIP3/ANXA2/TFEB axis, providing new target for treatment.

Language: Английский

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