Anti-inflammatory and immunomodulatory effects of the extracellular vesicles derived from human umbilical cord mesenchymal stem cells on osteoarthritis via M2 macrophages

Journal of Nanobiotechnology, Journal Year: 2022, Volume and Issue: 20(1)

Published: Jan. 20, 2022

Osteoarthritis (OA) is a degenerative illness that greatly impacts the life quality of patients. Currently, therapeutic approaches for OA are very limited in clinical. The extracellular vesicles (EVs) derived from different mesenchymal stem cells displayed prominent effect on OA. But most EVs have resources and risks host rejection, immunological response, etc. Human umbilical cord (hUCMSCs) hold advantages easy availability, minimal immune excellent immunomodulatory effects, although hUCMSCs-EVs seldom been applied Herein, we investigated potential anti-inflammatory effects treatment In our results, promoted polarization M2-type macrophages expression anti-inflammation-related cytokines (IL-10). Notably, supernate M2 induced by inhibited level inflammation-associated factors chondrocytes caused IL-1β. Further, injection articular lumen ameliorated progression exerted chondroprotective based joint model created surgical transection anterior cruciate ligament (ACLT). addition, found five highly enriched miRNAs hUCMSCs-EVs, including has-miR-122-5p, has-miR-148a-3p, has-miR-486-5p, has-miR-let-7a-5p, has-miR-100-5p High-throughput sequencing miRNAs, with targeted genes mainly PI3K-Akt signaling pathway. Furthermore, also detected protein abundance using liquidation chromatography tandem quadrupole mass spectrometry (LC-MS/MS) analysis. Thus, study indicates can alleviate cartilage degradation during progression, mechanically may through delivering key proteins modulating pathway mediated to promote macrophage, exhibiting potent potential. current findings suggest might serve as new reagent therapy

Language: Английский

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Immunomodulatory Mechanisms and Therapeutic Potential of Mesenchymal Stem Cells

Stem Cell Reviews and Reports, Journal Year: 2023, Volume and Issue: 19(5), P. 1214 - 1231

Published: April 14, 2023

Abstract Mesenchymal stem cells (MSCs) are regarded as highly promising for allogeneic cell therapy, owing to their multipotent nature and ability display potent varied functions in different diseases. The of MSCs, including native immunomodulation, high self-renewal characteristic, secretory trophic properties, can be employed improve the immune-modulatory MSCs impact most immune by directly contacting and/or secreting positive microenvironmental factors influence them. Previous studies have reported that immunomodulatory role is basically dependent on secretion from MSCs. This review discusses capabilities strategies successfully potential utilization clinical research. Graphical

Language: Английский

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Human umbilical cord mesenchymal stromal cell-derived exosomes protect against MCD-induced NASH in a mouse model

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

Published: Nov. 12, 2022

Abstract Background and aims Human umbilical cord mesenchymal stem cells (hUC-MSCs) are increasingly being studied in clinical trials of end-stage liver disease because their good tissue repair anti-inflammatory effects. hUC-MSC exosomes vesicles with spherical structures secreted by that produce them. The diameter is much smaller than hUC-MSCs, suggesting might be a novel safer therapeutic product cells. As have been suggested to biochemical functions similar those this study investigated the efficiency hUC-MSC-derived protecting against nonalcoholic steatohepatitis using an MCD-induced mouse model. Methods cell-derived were extracted purified. effect these on progression model was investigated. Results results showed UC-MSC intravenously transplanted into mice NASH improved body weight loss damage Additionally, inflammatory cytokines reduced, which may caused exosome-induced macrophage phenotypes both vitro vivo. In addition, reversed PPARα level ox-LDL-treated hepatocytes liver, had downregulated. Conclusions alleviate regulating phenotype macrophages reversing protein expression cells, holds great potential therapy.

Language: Английский

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Exosomes Derived From Umbilical Cord Mesenchymal Stem Cells Treat Cutaneous Nerve Damage and Promote Wound Healing

Frontiers in Cellular Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: June 30, 2022

Wound repair is a key step in the treatment of skin injury caused by burn, surgery, and trauma. Various stem cells have been proven to promote wound healing regeneration as candidate seed cells. Therefore, exosomes derived from are emerging promising method for repair. However, mechanism which still unclear. In this study, we reported that umbilical cord mesenchymal (UC-MSCs) treating cutaneous nerve damage. The results revealed UC-MSCs (UC-MSC-Exo) growth migration dermal fibroblast vitro culture, fibroblasts could secrete factors when stimulated exosomes. During process UC-MSC-Exo accelerated recruitment at site trauma significantly enhanced vivo. Interestingly, it was found recruiting fibroblasts, stimulating them (NGFs) promoting regeneration. concluded repair, may play an important role

Language: Английский

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Function and mechanism of mesenchymal stem cells in the healing of diabetic foot wounds

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: March 16, 2023

Diabetes has become a global public health problem. Diabetic foot is one of the most severe complications diabetes, which often places heavy economic burden on patients and seriously affects their quality life. The current conventional treatment for diabetic can only relieve symptoms or delay progression disease but cannot repair damaged blood vessels nerves. An increasing number studies have shown that mesenchymal stem cells (MSCs) promote angiogenesis re-epithelialization, participate in immune regulation, reduce inflammation, finally ulcer (DFU), rendering it an effective means treating disease. Currently, used are divided into two categories: autologous allogeneic. They mainly derived from bone marrow, umbilical cord, adipose tissue, placenta. MSCs different sources similar characteristics subtle differences. Mastering features to better select use premise improving therapeutic effect DFU. This article reviews types molecular mechanisms functions DFU provide innovative ideas using treat wound healing.

Language: Английский

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Human umbilical cord-derived mesenchymal stem cell transplantation supplemented with curcumin improves the outcomes of ischemic stroke via AKT/GSK-3β/β-TrCP/Nrf2 axis

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: Feb. 24, 2023

Abstract Background Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) engraftment is a promising therapy for acute ischemic stroke (AIS). However, the harsh microenvironment limits therapeutic efficacy of hUC-MSC therapy. Curcumin an anti-inflammatory agent that could improve inflammatory microenvironment. whether it enhances neuroprotective transplantation still unknown. In present study, we investigated and possible mechanism combined curcumin treatment in AIS. Methods Middle cerebral artery occlusion (MCAO) mice oxygen glucose deprivation (OGD) microglia were administrated hUC-MSCs with or without curcumin. Neurological deficits assessment, brain water content TTC used to assess effects treatment. To elucidate mechanism, MCAO OGD treated AKT inhibitor MK2206, GSK3β activator sodium nitroprusside (SNP), TDZD-8 Nrf2 gene knockout used. Immunofluorescence, flow cytometric analysis, WB RT-PCR evaluate polarization expression typical oxidative mediators, cytokines AKT/GSK-3β/β-TrCP/Nrf2 pathway protein. Results Compared solo hUC-MSC-grafted groups, curcumin-hUC-MSC significantly improved functional performance outcomes, diminished infarct volumes edema. The promoted via decreased ROS, mediators pro-inflammatory cytokines, while elevating cytokines. abolished antioxidant stress anti-inflammation mediated Moreover, enhanced phosphorylation GSK3β, inhibited β-TrCP nucleus translocation, accompanied activation nucleus. MK2206 activated suppressed nucleus, whereas reversed these phenomena. Furthermore, followed by inhibition restricted accumulation, which facilitated expression. Conclusions We have demonstrated exerts axis neurological function after

Language: Английский

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Progress and emerging techniques for biomaterial-based derivation of mesenchymal stem cells (MSCs) from pluripotent stem cells (PSCs)

Biomaterials Research, Journal Year: 2023, Volume and Issue: 27(1)

Published: Feb. 9, 2023

Abstract The use of mesenchymal stem cells (MSCs) for clinical purposes has skyrocketed in the past decade. Their multilineage differentiation potentials and immunomodulatory properties have facilitated discovery therapies various illnesses. MSCs can be isolated from infant adult tissue sources, which means they are easily available. However, this raises concerns because heterogeneity among MSC limits their effective use. Variabilities arise donor- tissue-specific differences, such as age, sex, source. Moreover, adult-sourced limited proliferation potentials, hinders long-term therapeutic efficacy. These limitations prompted researchers to develop a new method generating MSCs. Pluripotent (PSCs), embryonic induced PSCs (iPSCs), differentiate into types cells. Herein, thorough review characteristics, functions, importance is presented. existing sources MSCs, including adult- infant-based compared. most recent techniques deriving iPSCs, with focus on biomaterial-assisted methods both two- three-dimensional culture systems, listed elaborated. Finally, several opportunities improved efficiently producing aim advancing applications described.

Language: Английский

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Mesenchymal Stem Cells in the Pathogenesis and Therapy of Autoimmune and Autoinflammatory Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(22), P. 16040 - 16040

Published: Nov. 7, 2023

Mesenchymal stem cells (MSCs) modulate immune responses and maintain self-tolerance. Their trophic activities regenerative properties make them potential immunosuppressants for treating autoimmune autoinflammatory diseases. MSCs are drawn to sites of injury inflammation where they can both reduce contribute tissue regeneration. An increased understanding the role in development progression disorders has revealed that passive targets inflammatory process, becoming impaired by it exhibiting loss immunomodulatory activity. have been considered as novel cell therapies severe diseases, which at present only disease modifying rather than curative treatment options. emerging Clinical application rare cases other existing modalities failed, demonstrated use multiple including rheumatoid arthritis, systemic lupus erythematosus, myocardial infarction, liver cirrhosis, spinal cord injury, sclerosis, COVID-19 pneumonia. This review explores biological mechanisms behind It also covers their capabilities, therapeutic applications, challenges risks associated with MSC therapy.

Language: Английский

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Clinical Trials Targeting Secondary Damage after Traumatic Spinal Cord Injury

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3824 - 3824

Published: Feb. 14, 2023

Spinal cord injury (SCI) often causes loss of sensory and motor function resulting in a significant reduction quality life for patients. Currently, no therapies are available that can repair spinal tissue. After the primary SCI, an acute inflammatory response induces further tissue damage process known as secondary injury. Targeting to prevent additional during subacute phases SCI represents promising strategy improve patient outcomes. Here, we review clinical trials neuroprotective therapeutics expected mitigate injury, focusing primarily on those last decade. The strategies discussed broadly categorized acute-phase procedural/surgical interventions, systemically delivered pharmacological agents, cell-based therapies. In addition, summarize potential combinatorial considerations.

Language: Английский

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Amelioration of diabetic nephropathy in mice by a single intravenous injection of human mesenchymal stromal cells at early and later disease stages is associated with restoration of autophagy

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

Published: March 5, 2024

Abstract Background and aims Mesenchymal stromal cells (MSCs) a potentially effective disease-modulating therapy for diabetic nephropathy (DN) but their clinical translation has been hampered by incomplete understanding of the optimal timing administration in vivo mechanisms action. This study aimed to elucidate reno-protective potency associated single intravenous injections human umbilical cord-derived MSCs (hUC-MSCs) following shorter longer durations diabetes. Methods A streptozotocin (STZ)-induced model diabetes DN was established C57BL/6 mice. In groups animals, (h)UC-MSCs or vehicle were injected intravenously at 8 16 weeks after STZ along with vehicle-injected non-diabetic animals. Diabetes-related kidney abnormalities analyzed 2 later urine serum biochemical assays, histology, transmission electron microscopy immunohistochemistry. Serum concentrations pro-inflammatory pro-fibrotic cytokines quantified ELISA. The expression autophagy-related proteins within renal cortices investigated immunoblotting. Bio-distribution hUC-MSCs other organs evaluated mice injection fluorescent-labelled cells. Results Compared controls, had increases albumin creatinine ratio (uACR), mesangial matrix deposition, podocyte foot process effacement, glomerular basement membrane thickening interstitial fibrosis as well reduced numbers both 10 18 STZ. Early (8 weeks) hUC-MSC uACR improvements multiple IL-6, TNF-α, TGF-β1 compared Later (16 also resulted reduction diabetes-associated not IL-6 TNF-α. At time-points, kidneys higher p-mTOR mTOR, increased abundance p62, lower ULK1 Atg12, LC3B LC3A consistent suppression autophagy. These changes largely reversed hUC-MSC-injected contrast, neither early nor effects on blood glucose body weight Small CM-Dil-labeled remained detectable kidneys, lungs liver 14 days injection. Conclusions Single ameliorated mouse STZ-induced without affecting hyperglycemia, whether administered relatively short duration circulating restoration intra-renal Graphical abstract

Language: Английский

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