Cellular therapeutics and immunotherapies in wound healing – on the pulse of time?

Military Medical Research, Journal Year: 2024, Volume and Issue: 11(1)

Published: April 18, 2024

Abstract Chronic, non-healing wounds represent a significant challenge for healthcare systems worldwide, often requiring human and financial resources. Chronic arise from the complex interplay of underlying comorbidities, such as diabetes or vascular diseases, lifestyle factors, genetic risk profiles which may predispose extremities to local ischemia. Injuries are further exacerbated by bacterial colonization formation biofilms. Infection, consequently, perpetuates chronic inflammatory microenvironment, preventing progression completion normal wound healing. The current standard care (SOC) involves surgical debridement along with localized irrigation, requires inpatient under general anesthesia. This could be followed by, if necessary, defect coverage via reconstructive ladder utilizing skin graft, local, free flap techniques once conditions stabilized adequate blood supply is restored. To promote physiological healing, variety approaches have been subjected translational research. Beyond conventional healing drugs devices that currently supplement treatments, cellular immunotherapies emerged promising therapeutics can behave tailored therapies cell- molecule-specific properties. However, in contrast clinical omnipresence disorders, there remains shortage studies condensing body evidence on wounds. review provides comprehensive exploration therapies, experimental approaches, studies, offering insights into their efficacy limitations. Ultimately, we hope this line research serve an evidence-based foundation guide optimize patient long-term.

Language: Английский

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Cooperation between inhibitory immune checkpoints of senescent cells with immunosuppressive network to promote immunosenescence and the aging process

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102694 - 102694

Published: Feb. 1, 2025

Language: Английский

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Extracellular Vesicles in Organ Fibrosis: Mechanisms, Therapies, and Diagnostics

Cells, Journal Year: 2021, Volume and Issue: 10(7), P. 1596 - 1596

Published: June 25, 2021

Fibrosis is the unrelenting deposition of excessively large amounts insoluble interstitial collagen due to profound matrigenic activities wound-associated myofibroblasts during chronic injury in diverse tissues and organs. It a highly debilitating pathology that affects millions people globally leads decreased function vital organs increased risk cancer end-stage organ disease. Extracellular vesicles (EVs) produced within wound environment have emerged as important vehicles for conveying pro-fibrotic signals between many cell types involved driving fibrotic response. On other hand, EVs from sources such stem cells, uninjured parenchymal circulation vitro vivo anti-fibrotic provided novel much-needed therapeutic options. Finally, body fluids individuals contain cargo components may utility fibrosis biomarkers, which could circumvent current obstacles measurement clinic, allowing stage, progression, or regression be determined manner accurate, safe, minimally-invasive, conducive repetitive testing. This review highlights rapid recent progress our understanding EV-mediated pathogenesis, therapy, staging lung, kidney, heart, liver, pancreas, skin.

Language: Английский

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Professional killers: The role of extracellular vesicles in the reciprocal interactions between natural killer, CD8+ cytotoxic T‐cells and tumour cells

Journal of Extracellular Vesicles, Journal Year: 2021, Volume and Issue: 10(6)

Published: April 1, 2021

Abstract Extracellular vesicles (EVs) mediate the cross‐talk between cancer cells and of surrounding Tumour Microenvironment (TME). Professional killer include Natural Killer (NK) CD8+ Cytotoxic T‐lymphocytes (CTLs), which represent some most effective immune defense mechanisms against cells. Recent evidence supports role EVs released by NK CTLs in killing cells, paving road to a possible therapeutic for such EVs. This review article provides state‐of‐the‐art knowledge on NK‐ CTL‐derived as anticancer agents, focusing different functions sub‐types We also reviewed current effects cancer‐derived CTLs, identifying areas future investigation emerging new field EV‐mediated immunotherapy cancer.

Language: Английский

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Diagnostic and prognostic potential of the proteomic profiling of serum-derived extracellular vesicles in prostate cancer

Cell Death and Disease, Journal Year: 2021, Volume and Issue: 12(7)

Published: June 21, 2021

Abstract Extracellular vesicles (EVs) and their cargo represent an intriguing source of cancer biomarkers for developing robust sensitive molecular tests by liquid biopsy. Prostate (PCa) is still one the most frequent deadly tumor in men analysis EVs from biological fluids PCa patients has proven feasibility unprecedented potential such approach. Here, we exploited antibody-based proteomic technology, i.e. Reverse-Phase Protein microArrays (RPPA), to measure key antigens activated signaling isolated sera patients. Notably, found tumor-specific protein profiles associated with clinical settings as well candidate markers EV-based diagnosis. Among others, PD-L1, ERG, Integrin-β5, Survivin, TGF-β, phosphorylated-TSC2 partners MAP-kinase mTOR pathways emerged differentially expressed endpoints tumor-derived EVs. In addition, retrospective a 15-year follow-up cohort generated signature prognostic significance. Our results confirm that serum-derived EV may be improve current diagnostic procedures while providing predictive information. The approach proposed here been already applied entities other than PCa, thus proving its value translational medicine paving way innovative, clinically meaningful tools.

Language: Английский

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MRTF-A-NF-κB/p65 axis-mediated PDL1 transcription and expression contributes to immune evasion of non-small-cell lung cancer via TGF-β

Experimental & Molecular Medicine, Journal Year: 2021, Volume and Issue: 53(9), P. 1366 - 1378

Published: Sept. 1, 2021

PD-L1 is abnormally regulated in many cancers and critical for immune escape. Fully understanding the regulation of expression vital improving clinical efficacy relevant anticancer agents. TGF-β plays an important role low reactivity PD-1/PD-L1 antibody immunotherapy. However, it not very clear whether how affects expression. In present study, we show that upregulates transcriptional coactivator MRTF-A non-small-cell lung cancer cells, which subsequently interacts with NF-κB/p65 rather than SRF to facilitate binding PDL1 promoter, thereby activating transcription PD-L1. This leads escape NSCLC cells. process dependent on activation signaling pathway. vivo, inhibition effectively suppresses growth tumor syngrafts enrichment NK T cells tissue. Our study defines a new pathway regulates upon treatment, may have significant impact research into application immunotherapy treating cancer.

Language: Английский

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Molecular Mechanisms and Physiological Changes behind Benign Tracheal and Subglottic Stenosis in Adults

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2421 - 2421

Published: Feb. 22, 2022

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS considered to be the result of aberrant wound-healing process that leads fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology main cause subglottic or tracheal stenosis, also autoimmune infectious diseases may involved in causing LTS. Furthermore, obstruction anatomic region under glottis can diagnosed without apparent after comprehensive workup; this case, pathological called idiopathic (iSGS). So far, laryngotracheal scar resulting airway injury due was as inert tissue requiring surgical removal restore patency. However, assumption has recently been revised by regarding scarring fibroinflammatory event immunological alteration, similar other diseases. Recent acquisitions suggest factors, such growth cytokines, altered fibroblast function genetic susceptibility, all interact way leading wound healing an insult acts trigger. physiological derangement could play role promoting dysregulated response laryngo-tracheal mucosal injury, through biomechanical stress mechanotransduction activation. The aim narrative review present state-of-the-art knowledge molecular mechanisms, well mechanical physio-pathological features behind

Language: Английский

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Extracellular vesicle PD-L1 in reshaping tumor immune microenvironment: biological function and potential therapy strategies

Cell Communication and Signaling, Journal Year: 2022, Volume and Issue: 20(1)

Published: Jan. 28, 2022

Abstract Programmed cell death 1 ligand (PD-L1) is the for programmed protein-1 (PD-1), associated with immunosuppression. Signaling via PD-1/PD-L1 will transmits negative regulatory signals to T cells, inducing T-cell inhibition, reducing CD8 + proliferation, or promoting apoptosis, which effectively reduces immune response and leads large-scale tumor growth. Accordingly, many antibody preparations targeting PD-1 PD-L1 have been designed block binding of these two proteins restore proliferation cytotoxicity cells. However, drugs are ineffective in clinical practice. Recently, numerous studies shown that, addition surface also found on extracellular vesicles secreted by Extracellular vesicle can interact leading immunosuppression, has proposed as a potential mechanism underlying PD-1/PD-L1-targeted drug resistance. Therefore, it important explore production, regulation immunosuppression cells vesicles, well application biomarkers therapeutic targets.

Language: Английский

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TGF-β1 induced autophagy in cancer associated fibroblasts during hypoxia contributes EMT and glycolysis via MCT4 upregulation

Experimental Cell Research, Journal Year: 2022, Volume and Issue: 417(1), P. 113195 - 113195

Published: May 11, 2022

Language: Английский

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PD-1/PD-L1 axis in organ fibrosis

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

Published: May 19, 2023

Fibrosis is a pathological tissue repair activity in which many myofibroblasts are activated and extracellular matrix excessively accumulated, leading to the formation of permanent scars finally organ failure. A variety organs, including lung, liver, kidney, heart, skin, can undergo fibrosis under stimulation various exogenous or endogenous pathogenic factors. At present, pathogenesis still not fully elucidated, but it known that immune system plays key role initiation progression fibrosis. Immune checkpoint molecules regulators maintain tolerance homeostasis, among programmed cell death protein 1/programmed ligand 1 (PD-1/PD-L1) axis has attracted much attention. The exciting achievements tumor immunotherapy targeting PD-1/PD-L1 provide new insights into its use as therapeutic target for other diseases. In recent years, been preliminarily explored, further confirming close relationship signaling, regulation, This review discusses structure, expression, function, regulatory mechanism PD-1 PD-L1, summarizes research progress signaling fibrotic

Language: Английский

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