Mesenchymal stem cell secretome for regenerative medicine: Where do we stand?

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: 70, P. 103 - 124

Published: May 9, 2024

Mesenchymal stem cell (MSC)-based therapies have yielded beneficial effects in a broad range of preclinical models and clinical trials for human diseases. In the context MSC transplantation, it is widely recognized that main mechanism regenerative potential MSCs not their differentiation, with vivo data revealing transient low engraftment rates. Instead, therapeutic are mainly attributed to its secretome, i.e., paracrine factors secreted by these cells, further offering more attractive innovative approach due effectiveness safety cell-free product. this review, we will discuss benefits MSC-derived secretome medicine particular focus on respiratory, hepatic, neurological Both free vesicular be detailed. We also address novel strategies capable improving healing potential, namely delivering important molecules according specific diseases tissue needs, as well non-clinical studies allow us dissect mechanisms action. includes both soluble non-soluble factors, organized extracellular vesicles (EVs). Importantly, besides depending origin, characteristics deeply influenced external stimuli, highlighting possibility optimizing through preconditioning approaches. Nevertheless, clarity around action remains ambiguous, whereas need standardized procedures successful translation those products clinics urges.

Language: Английский

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Regulation of myofibroblast dedifferentiation in pulmonary fibrosis

Respiratory Research, Journal Year: 2024, Volume and Issue: 25(1)

Published: July 18, 2024

Abstract Idiopathic pulmonary fibrosis is a lethal, progressive, and irreversible condition that has become significant focus of medical research due to its increasing incidence. This rising trend presents substantial challenges for patients, healthcare providers, researchers. Despite the escalating burden fibrosis, available therapeutic options remain limited. Currently, United States Food Drug Administration approved two drugs treatment fibrosis—nintedanib pirfenidone. However, their effectiveness limited, they cannot reverse process. Additionally, these are associated with side effects. Myofibroblasts play central role in pathophysiology significantly contributing progression. Consequently, strategies aimed at inhibiting myofibroblast differentiation or promoting dedifferentiation hold promise as effective treatments. review examines regulation dedifferentiation, exploring various signaling pathways, regulatory targets, potential pharmaceutical interventions could provide new directions development.

Language: Английский

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Human umbilical cord/placenta mesenchymal stem cell conditioned medium attenuates intestinal fibrosis in vivo and in vitro

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

Published: March 7, 2024

Abstract Background A significant unmet need in inflammatory bowel disease is the lack of anti-fibrotic agents targeting intestinal fibrosis. This study aimed to investigate anti-fibrogenic properties and mechanisms conditioned medium (CM) from human umbilical cord/placenta-derived mesenchymal stem cells (UC/PL-MSC-CM) a murine fibrosis model primary myofibroblasts (HIMFs). Methods UC/PL-MSC-CM was concentrated 15-fold using 3 kDa cut-off filter. C57BL/6 mice aged 7 weeks old were randomly assigned one four groups: (1) control, (2) dextran sulfate sodium (DSS), (3) DSS + CM (late-phase treatment), (4) (early-phase treatment). Chronic colitis induced by three cycles administration. One cycle consisted days oral administration (1.75%, 2%, 2.5% DSS), followed 14 drinking water. intraperitoneally administered late phase (from day 50, 10 times) or early 29, cycles. HIMFs treated with TGF-β1 co-treated (10% culture media) cellular model. Results In animal study, reduced submucosa/muscularis propria thickness collagen deposition, which improved chronic colitis. The significantly expressions procollagen1A1 α-smooth muscle actin, elevated. effect more apparent UC-MSC-CM early-phase treatment procollagen1A1, fibronectin, actin expression downregulated fibrogenesis suppressing RhoA, MRTF-A, SRF expression. Conclusions Human inhibits TGF-β1-induced fibrogenic activation blocking Rho/MRTF/SRF pathway colitis-induced Thus, it may be regarded as novel candidate for cell-based therapy

Language: Английский

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Fibroblast Activation Protein Alpha (FAPα) in Fibrosis: Beyond a Perspective Marker for Activated Stromal Cells?

Biomolecules, Journal Year: 2023, Volume and Issue: 13(12), P. 1718 - 1718

Published: Nov. 29, 2023

The development of tissue fibrosis is a complex process involving the interaction multiple cell types, which makes search for antifibrotic agents rather challenging. So far, myofibroblasts have been considered key type that mediated and thus was main target therapy. However, current strategies aimed at inhibiting myofibroblast function or eliminating them fail to demonstrate sufficient effectiveness in clinical practice. Therefore, today, there an unmet need more reliable cellular targets contribute resolution inhibition its progression. Activated stromal cells, capable active proliferation invasive growth into healthy tissue, appear be such population due their accessible localization high susceptibility various regulatory signals. This subpopulation marked by fibroblast activation protein alpha (FAPα). For long time, FAPα exclusively marker cancer-associated fibroblasts. accumulating data are emerging on diverse functions FAPα, suggests this not only but also plays important role review aims summarize expression, regulation, regarding identify promising advances area.

Language: Английский

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Revisiting the role of MicroRNAs in the pathogenesis of idiopathic pulmonary fibrosis

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Oct. 16, 2024

Idiopathic pulmonary fibrosis (IPF) is a prevalent chronic disease characterized by alveolar epithelial cell damage, fibroblast proliferation and activation, excessive extracellular matrix deposition, abnormal epithelial-mesenchymal transition (EMT), resulting in tissue remodeling irreversible structural distortion. The mortality rate of IPF very high, with median survival time 2–3 years after diagnosis. exact cause remains unknown, but increasing evidence supports the central role epigenetic changes, particularly microRNA (miRNA), IPF. Approximately 10% miRNAs lung exhibit differential expression compared to normal tissue. Diverse miRNA phenotypes exert either pro-fibrotic or anti-fibrotic influence on progression In context IPF, factors such as DNA methylation long non-coding RNAs (lncRNAs) regulate differentially expressed miRNAs, which turn modulate various signaling pathways implicated this process, including transforming growth factor-β1 (TGF-β1)/Smad, mitogen-activated protein kinase (MAPK), phosphatidylinositol-3-kinase/protein B (PI3K/AKT) pathways. Therefore, review presents epidemiology discusses multifaceted regulatory roles explores impact through pathways, TGF-β1/Smad pathway its constituent structures. Consequently, we investigate potential for targeting treatment thereby contributing advancements research.

Language: Английский

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Cell therapy: A beacon of hope in the battle against pulmonary fibrosis

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(2)

Published: Jan. 28, 2025

Abstract Pulmonary fibrosis (PF) is a chronic and progressive interstitial lung disease characterized by abnormal activation of myofibroblasts pathological remodeling the extracellular matrix, with poor prognosis limited treatment options. Lung transplantation currently only approach that can extend life expectancy patients; however, its applicability severely restricted due to donor shortages patient‐specific limitations. Therefore, search for novel therapeutic strategies imperative. In recent years, stem cells have shown great promise in field regenerative medicine their self‐renewal capacity multidirectional differentiation potential, growing body literature supports efficacy cell therapy PF treatment. This paper systematically summarizes research progress various types PF. Furthermore, it discusses primary methods clinical outcomes PF, based on both preclinical data. Finally, current challenges key factors consider are objectively analyzed, future directions improving this proposed, providing new insights references patients.

Language: Английский

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Advances in locally administered nucleic acid therapeutics

Bioactive Materials, Journal Year: 2025, Volume and Issue: 49, P. 218 - 254

Published: March 10, 2025

Language: Английский

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Intermittent hypoxia-reoxygenation-induced miRNAs inhibit expression of IRF and interferon genes but activate NF-κB and expression of pulmonary fibrosis markers in human small airway epithelial cells

Life Sciences, Journal Year: 2025, Volume and Issue: unknown, P. 123569 - 123569

Published: March 1, 2025

Language: Английский

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Endothelial cells microRNAs participation in the angiogenesis regulation

Регенерация органов и тканей., Journal Year: 2025, Volume and Issue: 2(2), P. 59 - 81

Published: March 22, 2025

The 20th century marked the understanding that more than 80% of genes have an additional biological function in cell associated with regulation expression other genes. Non-coding sequential-type RNA regulators, including microRNAs, capable changing proteins cell, can be expressed such MicroRNAs are singlestranded sequences 20–25 nucleotides length regulate gene at posttranscriptional level through degradation or repression mRNA translation. This review examines aspects biogenesis microRNAs mammalian cells, as well their functions endothelial cells and angiogenesis.

Language: Английский

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Effect of Human Macrophage Conditioned Media on TGF-β-Induced Differentiation of Lung Fibroblasts

Bulletin of Experimental Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Language: Английский

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