Stem Cell Therapy in Inflammatory Bowel Disease: A Review of Achievements and Challenges

Journal of Inflammation Research, Год журнала: 2023, Номер Volume 16, С. 2089 - 2119

Опубликована: Май 1, 2023

Abstract: Inflammatory bowel disease (IBD), including Crohn's (CD) and ulcerative colitis (UC), is a group of chronic inflammatory diseases the gastrointestinal tract. Repeated inflammation can lead to complications, such as intestinal fistula, obstruction, perforation, bleeding. Unfortunately, achieving durable remission mucosal healing (MH) with current treatments difficult. Stem cells (SCs) have potential modulate immunity, suppress inflammation, anti-apoptotic pro-angiogenic effects, making them an ideal therapeutic strategy target damage in IBD. In recent years, hematopoietic stem (HSCs) adult mesenchymal (MSCs) shown efficacy treating addition, numerous clinical trials evaluated efficiency MSCs disease. This review summarizes research progress on safety SC-based therapy for IBD both preclinical models trials. We discuss mechanisms SC therapy, tissue repair, paracrine promotion angiogenesis, immune regulation, anti-inflammatory effects. also summarize engineering strategies aimed at enhancing immunosuppressive regenerative capabilities SCs diseases. Additionally, we highlight limitations future perspectives SC-related Graphic Keywords: cells, stromal HSCs, immunosuppression, disease, colitis,

Язык: Английский

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Overlapping Neuroimmune Mechanisms and Therapeutic Targets in Neurodegenerative Disorders

Biomedicines, Год журнала: 2023, Номер 11(10), С. 2793 - 2793

Опубликована: Окт. 14, 2023

Many potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases, such as Alzheimer's (AD) disease, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), well a seemingly distinct Niemann-Pick type C with primarily juvenile onset. This strongly argues for an overlap pathogenic mechanisms. The commonly researched include various cell subsets, microglia, peripheral macrophages, regulatory T cells (Tregs); the complement system; other soluble factors. In this review, we compare these diseases from clinical point of view highlight common pathways mechanisms protein aggregation, neurodegeneration, and/or neuroinflammation that could potentially lead to shared treatment strategies overlapping dysfunctions diseases. These approaches but not limited immunisation, cascade blockade, microbiome regulation, inhibition signal transduction, Treg boosting, stem transplantation.

Язык: Английский

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Research progress of engineered mesenchymal stem cells and their derived exosomes and their application in autoimmune/inflammatory diseases

Stem Cell Research & Therapy, Год журнала: 2023, Номер 14(1)

Опубликована: Апрель 11, 2023

Abstract Autoimmune/inflammatory diseases affect many people and are an important cause of global incidence mortality. Mesenchymal stem cells (MSCs) have low immunogenicity, immune regulation, multidifferentiation other biological characteristics, play role in tissue repair regulation widely used the research treatment autoimmune/inflammatory diseases. In addition, MSCs can secrete extracellular vesicles with lipid bilayer structures under resting or activated conditions, including exosomes, microparticles apoptotic bodies. Among them, as most component vesicles, function parent MSCs. Although their exosomes characteristics homing, engineering these through various technical means, such genetic engineering, surface modification further improve homing congenital make them specifically target specific tissues organs, therapeutic effect. This article reviews advanced technology MSC-derived its application some by searching literature published recent years at home abroad.

Язык: Английский

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Exosome-mediated miR-200a delivery into TGF-β-treated AGS cells abolished epithelial-mesenchymal transition with normalization of ZEB1, vimentin and Snail1 expression

Environmental Research, Год журнала: 2023, Номер 231, С. 116115 - 116115

Опубликована: Май 11, 2023

Язык: Английский

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Mesenchymal Stem Cell–Derived Exosomes in Various Chronic Liver Diseases: Hype or Hope?

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 171 - 189

Опубликована: Янв. 1, 2024

Abstract: Chronic liver conditions are associated with high mortality rates and have a large adverse effect on human well-being as well significant financial burden. Currently, the only effective treatment available for effects of failure cirrhosis resulting from progression several chronic diseases is transplantation carried out at original location. This implies that developing novel treatments imperative. Regenerative medicine has long been stem cell therapy. Mesenchymal cells (MSCs), type great differentiation potential, become preferred source According to recent studies, MSCs' paracrine products—rather than their capacity differentiation—play therapeutic effect. MSC exosomes, extracellular vesicle (MSC-EV), came into view substances MSCs. research, exosomes can maintain tissue homeostasis, which necessary healthy function. All tissues contain them, they take part in variety biological activities support cellular activity regeneration order preserve homeostasis. The outcomes use MSCs produce option range diseases. review provides brief overview MSC-EVs outlines physiological roles biochemical capabilities. elucidation role recovery repair hepatic tissues, contribution maintaining discussed relation different aims provide new insights unique play Keywords: mesenchymal cells, disease, immunomodulation, homeostasis

Язык: Английский

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Charge‐Reversed Exosomes for Targeted Gene Delivery to Cartilage for Osteoarthritis Treatment

Small Methods, Год журнала: 2024, Номер 8(9)

Опубликована: Апрель 12, 2024

Abstract Gene therapy has the potential to facilitate targeted expression of therapeutic proteins promote cartilage regeneration in osteoarthritis (OA). The dense, avascular, aggrecan‐glycosaminoglycan (GAG) rich negatively charged cartilage, however, hinders their transport reach chondrocytes effective doses. While viral vector mediated gene delivery shown promise, concerns over immunogenicity and tumorigenic side‐effects persist. To address these issues, this study develops surface‐modified cartilage‐targeting exosomes as non‐viral carriers for therapy. Charge‐reversed cationic are engineered mRNA by anchoring targeting optimally arginine‐rich motifs into anionic exosome bilayer using buffer pH a charge‐reversal switch. Cationic penetrated through full‐thickness early‐stage arthritic human owing weak‐reversible ionic binding with GAGs efficiently delivered encapsulated eGFP residing tissue deep layers, while unmodified do not. When intra‐articularly injected destabilized medial meniscus mice knees OA, loaded charge‐reversed overcame joint clearance rapidly creating an intra‐tissue depot expressing eGFP; native remained unsuccessful. thus hold strong translational platform technology cartilage‐targeted any relevant targets OA treatment.

Язык: Английский

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Extracellular vesicles from dental pulp mesenchymal stem cells modulate macrophage phenotype during acute and chronic cardiac inflammation in athymic nude rats with myocardial infarction

Inflammation and Regeneration, Год журнала: 2024, Номер 44(1)

Опубликована: Май 28, 2024

Abstract Background/aims Extracellular vesicles (EVs) derived from dental pulp mesenchymal stem cells (DP-MSCs) are a promising therapeutic option for the treatment of myocardial ischemia. The aim this study is to determine whether MSC-EVs could promote pro-resolving environment in heart by modulating macrophage populations. Methods EVs three independent biopsies DP-MSCs (MSC-EVs) were isolated tangential flow-filtration and size exclusion chromatography characterized omics analyses. Biological processes associated with these molecules analyzed using String GeneCodis platforms. immunomodulatory capacity polarize macrophages towards or M2-like phenotype was assessed evaluating surface markers, cytokine production, efferocytosis. potential evaluated an acute infarction (AMI) model nude rats. Infarct distribution populations infarct area 7 21 days after intramyocardial injection MSC-EVs. Results Lipidomic, proteomic, miRNA-seq analysis revealed their association biological involved tissue regeneration regulation immune system, among others. promoted differentiation pro-inflammatory phenotype, as evidenced increased expression M2 markers decreased secretion cytokines. Administration rats AMI limited extent infarcted at post-infarction. MSC-EV also reduced number within area, promoting resolution inflammation. Conclusion exhibited similar characteristics level irrespective biopsy which they derived. All exerted effective responses rat AMI, indicating agents inflammation AMI.

Язык: Английский

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Roles, Functions, and Pathological Implications of Exosomes in the Central Nervous System

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1345 - 1345

Опубликована: Фев. 5, 2025

Exosomes are a subset of extracellular vesicles (EVs) secreted by nearly all cell types and have emerged as novel mechanism for intercellular communication within the central nervous system (CNS). These facilitate transport proteins, nucleic acids, lipids, metabolites between neurons glial cells, playing pivotal role in CNS development maintenance homeostasis. Current evidence indicates that exosomes from cells may function either inhibitors or enhancers onset progression neurological disorders. Furthermore, been found to disease-related molecules across blood–brain barrier, enabling their detection peripheral blood. This distinctive property positions promising diagnostic biomarkers conditions. Additionally, growing body research suggests derived mesenchymal stem exhibit reparative effects context review provides concise overview functions both physiological pathological states, with particular emphasis on emerging roles potential therapeutic agents treatment diseases.

Язык: Английский

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Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying miRNA as a Potential Multi Target Therapy to COVID-19: an In Silico Analysis

Stem Cell Reviews and Reports, Год журнала: 2021, Номер 17(2), С. 341 - 356

Опубликована: Янв. 28, 2021

In the end of 2019 COVID-19 emerged as a new threat worldwide and this disease present impaired immune system, exacerbated production inflammatory cytokines, coagulation disturbs. Mesenchymal stem cell (MSC) derived extracellular vesicles (EVs) have therapeutic option due to its intrinsic properties alleviate responses, capable promote restoring injured tissue. EVs contain heterogeneous cargo, including active microRNAs, small noncoding sequences involved in post-transcriptional gene repression or degradation can attach multiple targets. This study investigated whether MSC-EVs miRNA cargo has capacity modulate death disturbs severe COVID-19. Through bioinformatics analysis, four datasets miRNA, using different tissue sources (bone marrow, umbilical cord adipose tissue), one dataset mRNA marrow) were analyzed. 58 miRNAs overlap Sequentially, those at least two datasets, analyzed miRWalk for 3'UTR binding target mRNA. The result predicted 258 cytokines chemokines, 266 genes 148 cascades. Some may simultaneously attenuate agents, inhibit key factors cascade, consequently preventing damage Therefore, MSC-derived their are potential multitarget approach able improve survival rates patients.

Язык: Английский

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MSC-Derived Small Extracellular Vesicles Attenuate Autoimmune Dacryoadenitis by Promoting M2 Macrophage Polarization and Inducing Tregs via miR-100-5p

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Июль 6, 2022

Background Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have been increasingly proved as promising immunomodulators against some autoimmune disorders. However, the possible effect and underlying mechanism of MSC-sEVs in dry eye rarely studied. Methods Small from human umbilical cord mesenchymal cells (hUC-MSC-sEVs) were subconjunctivally injected to rabbit model, their preventive or therapeutical effects assessed by recording clinical histological scores. Quantitative real-time PCR (Q-PCR), western blot flow cytometry performed evaluate immunomodulatory hUC-MSC-sEVs on macrophages T regulatory (Tregs) both vivo vitro , cell proliferation was detected Bromodeoxyuridine (BrdU) assay. In addition, high expression miR-100-5p identified Q-PCR, functional role sEVs-miR-100-5p explored a series co-culture experiments using sEVs derived hUC-MSCs transfected with inhibitor. Results We firstly demonstrated that had dacryoadenitis, an animal model Sjögren’s syndrome (SS) eye. Further investigation revealed administration effectively elicited into anti-inflammatory M2 phenotype elevated proportion Tregs which contributed reduced inflammation improved tissue damage. Importantly, hUC-MSC-sEVs-educated M2-like exhibited strong capacity inhibit CD4+ promote Treg generation . Mechanistically, highly enriched hUC-MSC-sEVs, knockdown partially blunted promotion macrophage polarization even attenuated suppression expansion. Conclusion Our data indicated alleviated dacryoadenitis promoting possibly through shuttling miR-100-5p. This study sheds new light application therapeutic method for SS

Язык: Английский

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