Mesenchymal stem cell extracellular vesicle vascularization bioactivity and production yield are responsive to cell culture substrate stiffness

Bioengineering & Translational Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Abstract Mesenchymal stem cell‐derived extracellular vesicles (MSC EVs) are an attractive therapeutic option for regenerative medicine applications due to their inherently pro‐angiogenic and anti‐inflammatory properties. However, reproducible cost‐effective production of highly potent MSC EVs is challenging, limiting translational potential. Here, we investigated whether the well‐characterized responsiveness MSCs mechanical environment—specifically, substrate stiffness—could be exploited generate with increased bioactivity without need biochemical priming or genetic manipulation. Using polydimethylsiloxane bone marrow‐derived (BM‐MSCs), show that decreasing stiffness substrates as low 3 kPa significantly improves measured by tube formation gap closure assays. We also demonstrate lower EV overall yield, important clinical translation. Furthermore, establish mechanoresponsiveness induced pluripotent (iMSC) comparability BM‐MSC EVs, again using With this data, confirm iMSCs' feasibility alternative, renewable cell source reduced donor variability. Overall, these results suggest utilizing a promising, simple, potentially scalable approach does not require exogenous cargo extraneous reagents EVs.

Language: Английский

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Exosome-based miRNA delivery: Transforming cancer treatment with mesenchymal stem cells

Regenerative Therapy, Journal Year: 2025, Volume and Issue: 28, P. 558 - 572

Published: Feb. 13, 2025

Language: Английский

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Batch variability and anti-inflammatory effects of iPSC-derived mesenchymal stromal cell extracellular vesicles in osteoarthritis in vitro model

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13

Published: April 2, 2025

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) hold promise as a cell-free therapy for osteoarthritis (OA), due to their immunomodulatory and anti-inflammatory properties. However, the need large-scale expansion obtain MSC-EVs clinical use can lead senescence-related changes loss of stem-like In this scenario, induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) offer unique opportunity address obstacles associated with traditional MSC-based therapies. This study used xeno-free (XFS) medium long-term both iMSCs, EVs comparison. Characterization cells was conducted across different passages, potential iEVs assessed using an in vitro model osteoarthritis. Long-term resulted cellular senescence reduction trilineage differentiation capacity by passage five, accompanied diminished properties EVs. On other hand, iMSCs exhibited batch-to-batch variability EV biological effects iMSC-EVs were prolonged compared MSC-EVs, providing wider window activity therapeutic purposes. Despite this, among iMSC batches poses challenges reliability OA treatment. Further work is needed overcome these limitations application.

Language: Английский

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Recent advances in the roles of extracellular vesicles in cardiovascular diseases: pathophysiological mechanisms, biomarkers, and cell-free therapeutic strategy

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: May 5, 2025

Abstract Cardiovascular diseases (CVDs) represent a profound challenge with inflammation playing significant role in their pathophysiology. Extracellular vesicles (EVs), which are membranous structures encapsulated by lipid bilayer, essential for intercellular communication facilitating the transport of specific bioactive molecules, including microRNAs, proteins, and lipids. Emerging evidence suggests that regulatory mechanisms governing cardiac resident cells influenced EVs, function as messengers thereby contribute to advancement CVDs. In this review, we discuss multifaceted biological functions EVs involvement pathogenesis various CVDs, encompassing myocardial infarction, ischemia–reperfusion injury, heart failure, atherosclerosis, myocarditis, cardiomyopathy, aneurysm. Furthermore, summarize recent advancements utilizing non-invasive biomarkers cell-free therapy based on diagnosis treatment Future research should investigate effective techniques isolation purification from body fluids, while also exploring pathways clinical translation EVs. Additionally, it is imperative identify appropriate EV-miRNA profiles or combinations present circulation patients, could serve improve diagnostic accuracy By synthesizing integrating findings, review aims provide innovative perspectives CVDs potential therapeutic strategies.

Language: Английский

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Neuron-Derived Extracellular Vesicles: Emerging Regulators in Central Nervous System Disease Progression

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: May 6, 2025

Language: Английский

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The application potential of iMSCs and iMSC-EVs in diseases

Frontiers in Bioengineering and Biotechnology, Journal Year: 2024, Volume and Issue: 12

Published: July 29, 2024

The immune system, functioning as the body's "defense army", plays a role in surveillance, defense. Any disruptions system can lead to development of immune-related diseases. Extensive researches have demonstrated crucial immunoregulatory mesenchymal stem cells (MSCs) these Of particular interest is ability induce somatic under specific conditions, generating new cell type with characteristics known induced pluripotent (iPSC). differentiation iPSCs into MSCs, specifically cell-derived (iMSCs), hold promise potential solution challenges potentially serving an alternative traditional drug therapies. Moreover, products iMSCs, termed extracellular vesicles (iMSC-EVs), may exhibit functions similar iMSCs. With biological advantages EVs, they become focus "cell-free therapy". Here, we provided comprehensive summary impact iMSCs on cells, explored applications and iMSC-EVs diseases, briefly discussed fundamental EVs. Finally, overviewed current associated iMSC-EVs. It our hope that this review related will contribute approaches for treatment

Language: Английский

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Enhanced Extracellular Vesicle Cargo Loading via microRNA Biogenesis Pathway Modulation

ACS Biomaterials Science & Engineering, Journal Year: 2024, Volume and Issue: 10(10), P. 6286 - 6298

Published: Sept. 21, 2024

Extracellular vesicles (EVs) are physiological vectors for the intercellular transport of a variety molecules. Among these, small RNAs, and especially microRNAs (miRNAs), have been identified as prevalent components, there has thus robust investigation EVs therapeutic miRNAs delivery. However, intrinsic levels EV-associated generally too low to enable efficient effective outcomes. We hypothesized that miRNA localization could be improved by limiting competing interactions occur throughout biogenesis process. Using miR-146a-5p model, modulation transcription, nuclear export, enzymatic cleavage steps were tested impact on EV loading. Working in HEK293T cells, various alterations pathway shown EVs. The system was then applied induced pluripotent stem cells (iPSCs), more promising substrate production, separated assessed anti-inflammatory efficacy

Language: Английский

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Exploration of Exosome Therapy for Diabetic Foot Ulcer

Advances in Clinical Medicine, Journal Year: 2024, Volume and Issue: 14(06), P. 1381 - 1387

Published: Jan. 1, 2024

Language: Английский

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[Research advances on stem cell-based treatments in animal studies and clinical trials of lymphedema].

PubMed, Journal Year: 2024, Volume and Issue: 38(1), P. 99 - 106

Published: Jan. 15, 2024

To summarize the progress of roles and mechanisms various types stem cell-based treatments their combination therapies in both animal studies clinical trials lymphedema.

Language: Английский

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