A comprehensive evaluation of stability and safety for HEK293F-derived extracellular vesicles as promising drug delivery vehicles DOI Creative Commons
Zhiqing Chen,

Tao-Tao Tang,

Ri‐Ning Tang

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown, P. 113673 - 113673

Published: March 1, 2025

Language: Английский

Extracellular Vesicle Heterogeneity and Its Impact for Regenerative Medicine Applications DOI Creative Commons
Simonides Immanuel van de Wakker,

Fleur Michelle Meijers,

Joost P. G. Sluijter

et al.

Pharmacological Reviews, Journal Year: 2023, Volume and Issue: 75(5), P. 1043 - 1061

Published: June 6, 2023

Extracellular vesicles (EVs) are cell-derived membrane enclosed particles that involved in physiological and pathological processes. EVs increasingly being studied for therapeutic applications the field of regenerative medicine. Therapeutic application stem has shown great potential to stimulate tissue repair. However, exact mechanisms through which they induce this effect not been fully clarified. This may a large extent be attributed lack knowledge on EV heterogeneity. Recent studies suggest represent heterogeneous population with distinct functions. The heterogeneity can differences their biogenesis, as such, classified into populations then further subcategorized various subpopulations. A better understanding is crucial elucidating action regeneration. review provides an overview latest insights related repair, including different characteristics contribute such heterogeneity, well functional among subtypes. It also sheds light challenges hinder clinical translation EVs. Additionally, innovative isolation techniques studying discussed. Improved active subtypes would promote development tailored therapies aid researchers EV-based therapeutics clinic. Significance Statement Within we discuss properties subpopulations, implications therapeutics. We aim provide new aspects leading preparations, stress importance applications.

Language: Английский

Citations

61

Engineered mesenchymal stem cell-derived extracellular vesicles: A state-of-the-art multifunctional weapon against Alzheimer's disease DOI Creative Commons
Tong Yin, Yan Liu, Wenbo Ji

et al.

Theranostics, Journal Year: 2023, Volume and Issue: 13(4), P. 1264 - 1285

Published: Jan. 1, 2023

With the increase of population aging, number Alzheimer's disease (AD) patients is also increasing.According to current estimates, approximately 11% people over 65 suffer from AD, and that percentage rises 42% among 85.However, no effective treatment capable decelerating or stopping AD progression available.Furthermore, AD-targeted drugs composed synthetic molecules pose concerns regarding biodegradation, clearance, immune response, neurotoxicity.Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are essential intercellular communication mediators holding great promise as therapeutics owing their biocompatibility, versatility, effortless storage, superior safety, ability transport messenger noncoding RNAs, proteins, lipids, DNAs, other bioactive compounds derived cells.The functionalisation engineering strategies MSC-EVs highlighted (e.g.preconditioning, drug loading, surface modification, artificial EV fabrication), which could improve by multiple therapeutic effects, including clearing abnormal protein accumulation achieving neuroprotection immunomodulatory effects.Herein, this review summarises state-of-the-art engineer MSC-EVs, discusses progress in use therapeutics, presents perspectives challenges associated with related clinical applications, concludes engineered show immense potential therapy.

Language: Английский

Citations

49

Stem cell- derived extracellular vesicles as new tools in regenerative medicine - Immunomodulatory role and future perspectives DOI Creative Commons
Elżbieta Karnas, Patrycja Dudek, Ewa Zuba‐Surma

et al.

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

Published: Jan. 24, 2023

In the last few decades, practical use of stem cells (SCs) in clinic has attracted significant attention regenerative medicine due to ability these proliferate and differentiate into other cell types. However, recent findings have demonstrated that therapeutic capacity SCs may also be mediated by their secrete biologically active factors, including extracellular vesicles (EVs). Such submicron circular membrane-enveloped released from surface harbour bioactive cargo form proteins, lipids, mRNA, miRNA, regulatory factors. Notably, growing evidence indicated EVs transfer content recipient greatly modulate functional fate. Thus, they been recently envisioned as a new class paracrine factors cell-to-cell communication. Importantly, activity immune system, playing an important role regulation inflammation, exhibiting broad spectrum immunomodulatory promotes transition pro-inflammatory pro-regenerative environment site tissue injury. Consequently, interest is placed on attempts utilize clinical applications inflammatory-related dysfunctions potential next-generation alternative cell-based approaches. this review we will discuss current knowledge biological properties SC-derived EVs, with special focus inflammatory response. We address several disease models, vitro vivo preclinical, well studies. Finally, highlight perspectives future challenges emerging EV-based strategies inflammation-related diseases treatment.

Language: Английский

Citations

36

Cell culture‐derived extracellular vesicles: Considerations for reporting cell culturing parameters DOI Creative Commons
Faezeh Shekari, Faisal J. Alibhai, Hossein Baharvand

et al.

Journal of Extracellular Biology, Journal Year: 2023, Volume and Issue: 2(10)

Published: Oct. 1, 2023

Abstract Cell culture‐conditioned medium (CCM) is a valuable source of extracellular vesicles (EVs) for basic scientific, therapeutic and diagnostic applications. culturing parameters affect the biochemical composition, release possibly function CCM‐derived EVs (CCM‐EV). The CCM‐EV task force Rigor Standardization Subcommittee International Society Extracellular Vesicles aims to identify relevant cell parameters, describe their effects based on current knowledge, recommend reporting outstanding questions. While some recommendations are valid all types, cell‐specific may need be established non‐mammalian sources, such as bacteria, yeast plant cells. Current progress towards these goals summarized in this perspective paper, along with checklist facilitate transparent improve reproducibility research.

Language: Английский

Citations

28

Mesenchymal Stem Cell Culture within Perfusion Bioreactors Incorporating 3D‐Printed Scaffolds Enables Improved Extracellular Vesicle Yield with Preserved Bioactivity DOI Creative Commons
Stephanie M. Kronstadt,

Divya B. Patel,

Louis J. Born

et al.

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(20)

Published: March 17, 2023

Abstract Extracellular vesicles (EVs) are implicated as promising therapeutics and drug delivery vehicles in various diseases. However, successful clinical translation will depend on the development of scalable biomanufacturing approaches, especially due to documented low levels intrinsic EV‐associated cargo that may necessitate repeated doses achieve benefit certain applications. Thus, here effects a 3D‐printed scaffold‐perfusion bioreactor system assessed production bioactivity EVs secreted from bone marrow‐derived mesenchymal stem cells (MSCs), cell type widely generating with therapeutic potential. The results indicate perfusion culture induces an ≈40‐80‐fold increase (depending measurement method) MSC EV compared conventional culture. Additionally, generated using significantly improve wound healing diabetic mouse model, increased CD31 + staining bed tissue animals treated flask culture‐generated EVs. Overall, this study establishes solution major translational bottleneck, capacity for tunability specific applications general improvement alongside advancements 3D‐printing technologies.

Language: Английский

Citations

27

Nanoparticle Tracking Analysis: An Effective Tool to Characterize Extracellular Vesicles DOI Creative Commons
Gabrielle Kowkabany, Yuping Bao

Molecules, Journal Year: 2024, Volume and Issue: 29(19), P. 4672 - 4672

Published: Oct. 1, 2024

Extracellular vesicles (EVs) are membrane-enclosed particles that have attracted much attention for their potential in disease diagnosis and therapy. However, the clinical translation is limited by dosing consistency due to heterogeneity. Among various characterization techniques, nanoparticle tracking analysis (NTA) offers distinct benefits EV characterization. In this review, we will discuss NTA technique with a focus on factors affecting results; then, review two modes of techniques along suitable applications specific areas studies. EVs typically characterized size, size distribution, concentration, protein markers, RNA cargos. The light-scattering mode accurate concentration information solution, which useful comparing isolation methods, storage conditions, secretion conditions. contrast, fluorescent allows differentiating subgroups based markers. success fluorescence heavily relies tags (e.g., types dyes labeling methods). When labeled disease-specific an effective tool detection biological fluids, such as saliva, blood, serum. Finally, limitations future directions

Language: Английский

Citations

14

Optimizing mesenchymal stem cell extracellular vesicles for chronic wound healing: Bioengineering, standardization, and safety DOI Creative Commons
Yusuke Shimizu, Edward Hosea Ntege, Yoshikazu Inoue

et al.

Regenerative Therapy, Journal Year: 2024, Volume and Issue: 26, P. 260 - 274

Published: June 1, 2024

Chronic wounds represent a significant global burden, afflicting millions with debilitating complications. Despite standard care, impaired healing persists due to factors like persistent inflammation and tissue regeneration. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) offer an innovative regenerative medicine approach, delivering cell-derived therapeutic cargo in engineered nanoscale delivery systems. This review examines pioneering bioengineering strategies engineer MSC-EVs into precision nanotherapeutics for chronic wounds. Emerging technologies CRISPR gene editing, microfluidic manufacturing, biomimetic systems are highlighted their potential enhance MSC-EV targeting, optimize enrichment, ensure consistent clinical-grade production. However, key hurdles remain, including batch variability, rigorous safety assessment tumorigenicity, immunogenicity, biodistribution profiling. Crucially, collaborative frameworks harmonizing regulatory science patient advocacy hold the expediting clinical translation. By overcoming these challenges, could catalyze new era of off-the-shelf therapies, restoring hope afflicted by non-healing

Language: Английский

Citations

10

The Role of the Notch Signaling Pathway in the Differentiation of Human Umbilical Cord-Derived Mesenchymal Stem Cells DOI Creative Commons
Wanhong Xing, Jianxin Yang,

Ying Zheng

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(2)

Published: Feb. 21, 2024

Human umbilical cord mesenchymal stem cells (hUCMSCs) exhibit potent self-renewal and multilineage differentiation characteristics. They have garnered substantial attention within the domain of regenerative medicine owing to their therapeutic potential, such as in tissue repair, regeneration, immunomodulation, anti-inflammation, angiogenesis, wound healing, neuroprotection, neuroregeneration. The process fate determination is initiated by multiple signaling molecules. During development homeostasis, Notch pathway assumes a pivotal function cell renewal cells. A growing body research has revealed that plays role hUCMSC proliferation differentiation. latest progress concerning crucial functions maintaining homeostasis determining hUCMSCs summarized. Furthermore, authors also summarized mediators related differentiation, well alterations mechanisms involved therapy.

Language: Английский

Citations

9

Enabling Mesenchymal Stromal Cells and Their Extracellular Vesicles Clinical Availability—A Technological and Economical Evaluation DOI Creative Commons
Ricardo Marques e Silva, Sara Sousa Rosa, José A. L. Santos

et al.

Journal of Extracellular Biology, Journal Year: 2025, Volume and Issue: 4(3)

Published: March 1, 2025

ABSTRACT Mesenchymal stromal cell‐derived extracellular vesicles (MSC‐EVs) have shown significant therapeutic potential across a wide range of clinical conditions, complementing the progress MSC‐based therapies, some which already received regulatory approval. However, high cost these therapies has limited their accessibility, creating an urgent need to explore manufacturing strategies that reduce goods and selling prices. This study presents design simulation scalable platform for co‐production clinical‐grade MSC MSC‐EVs using SuperPro Designer. Various production scenarios were evaluated maximise capacity while analysing impact on economic performance. Our findings demonstrate doses containing 10 11 particles, prices from 166 309€ 1659 3082€, respectively. For MSC, vary between 965 42,673€ depending dose size scale. Importantly, approach enables cost‐sharing products, contributing significantly lower compared individual production. Overall, proposed achieved attractive payback time 3 years return investment 36%. By increasing number staggered units, further price reductions improved metrics could be attained. In conclusion, this highlights deliver cost‐effective, advancing field regenerative medicine enhancing accessibility innovative treatments.

Language: Английский

Citations

1

Cellular expansion of MSCs: Shifting the regenerative potential DOI Creative Commons
Katherine R. Miclau, William S. Hambright, Johnny Huard

et al.

Aging Cell, Journal Year: 2022, Volume and Issue: 22(1)

Published: Dec. 19, 2022

Mesenchymal-derived stromal or progenitor cells, commonly called "MSCs," have attracted significant clinical interest for their remarkable abilities to promote tissue regeneration and reduce inflammation. Recent studies shown that MSCs' therapeutic effects, originally attributed the cells' direct differentiation capacity into of interest, are largely driven by biomolecules cells secrete, including cytokines, chemokines, growth factors, extracellular vesicles containing miRNA. This secretome coordinates upregulation endogenous repair immunomodulation in local microenvironment through crosstalk MSCs with host cells. Therapeutic applications secretome-derived products often involve vitro monolayer expansion. However, consecutive passaging significantly alters potential, inducing a broad shift from pro-regenerative pro-inflammatory phenotype. A consistent by-product expansion is onset replicative senescence, state cell arrest characterized an increased release proinflammatory cytokines factors. little known about changes profile at different stages Some culture conditions bioprocessing techniques promise more effectively retaining anti-inflammatory MSC phenotype throughout Understanding how influence nature function MSCs, associated secretome, may provide key insights underlying mechanisms driving these alterations. Elucidating dynamic diverse each stage critical next step development standardized, safe, effective MSC-based therapies.

Language: Английский

Citations

36