Towards a Continuous Production of Human Mesenchymal Stromal Cells in a Chemically Defined Medium: Opportunities and Challenges for a Robust and Scalable Expansion Process DOI
Lars Tasto, Denise Salzig

Cell engineering, Год журнала: 2023, Номер unknown, С. 379 - 427

Опубликована: Янв. 1, 2023

Язык: Английский

Immobilization: the promising technique to protect and increase the efficiency of microorganisms to remove contaminants DOI
Aya A. Najim, Ahmed Y. Radeef,

Ibrahim al‐Doori

и другие.

Journal of Chemical Technology & Biotechnology, Год журнала: 2024, Номер 99(8), С. 1707 - 1733

Опубликована: Март 8, 2024

Abstract Biodegradation of pollutants is one the most economical methods for their removal and usually accompanied by no production toxic by‐products. In general, this approach favored over others because it offers reduced expenses potential complete mineralization. order to enhance viability longevity bioremediation agents within polluted areas, becomes necessary immobilize cells. Cell immobilization refers procedure confining intact cells specific areas a device or material, without compromising essential biological functions. A wide variety carriers approaches have been used restriction various Immobilization techniques, such as microencapsulation, opened up new possibilities in biotechnology facilitating development artificial organs, cell therapies drug delivery systems. Researchers found promising outcomes applications through microorganisms. This enhances stability, reusability catalytic efficiency, making valuable strategy biocatalysis, other biotechnological processes. Notably, use immobilized microorganisms has led significant improvements pollutants, with some studies achieving 100% efficiency. When comparing degradation between free same time period, results demonstrated that achieved efficiency >21% more than microbial consortia. The primary objective review give an overview key scientific aspects related using cells, particular focus on techniques entrap © 2024 Society Chemical Industry (SCI).

Язык: Английский

Процитировано

23

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

и другие.

Regenerative Therapy, Год журнала: 2024, Номер 26, С. 260 - 274

Опубликована: Июнь 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

Язык: Английский

Процитировано

11

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

и другие.

Journal of Extracellular Biology, Год журнала: 2025, Номер 4(3)

Опубликована: Март 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.

Язык: Английский

Процитировано

1

A roadmap towards manufacturing extracellular vesicles for cardiac repair DOI
Ana F. Louro, Ana Meliciano, Paula M. Alves

и другие.

Trends in biotechnology, Год журнала: 2024, Номер 42(10), С. 1305 - 1322

Опубликована: Апрель 22, 2024

Язык: Английский

Процитировано

6

Process development for the production of mesenchymal stromal cell-derived extracellular vesicles in conventional 2D systems DOI Creative Commons

Jan Barekzai,

Laura Refflinghaus,

Maduwuike Okpara

и другие.

Cytotherapy, Год журнала: 2024, Номер 26(9), С. 999 - 1012

Опубликована: Апрель 27, 2024

BackgroundIn recent years, the importance of extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) has increased significantly. For their widespread use, a standardized EV manufacturing is needed which often includes conventional, static 2D systems. these system critical process parameters need to be determined.MethodsWe studied impact on MSC proliferation, MSC-derived particle production including EVs, EV- and MSC-specific marker expression, functionality in HaCaT cell migration assay.ResultsWe found that culture growth surface media affected MSCs secretory behavior. Interestingly, materials promoted proliferation did not necessarily result most functional particles. In addition, we seeded at 4 × 103 cm−2 produced particles with improved properties compared higher seeding densities. highly proliferative state produce particles, although were significantly more effective promoting migration. The same correlation was when investigating cultivation temperature. A physiological temperature 37°C optimal for yield, it resulted We observed proliferation-associated potential correlations between glucose consumption, enabling estimation final yields.ConclusionsOur findings suggest parameters, must defined prior each individual do require complex expensive equipment, can increase EVs. Integrating into development paves way robust efficient early clinical phases.Graphical abstract

Язык: Английский

Процитировано

4

Small Extracellular Vesicles from Breast Cancer Cells Induce Cardiotoxicity DOI Open Access
Jhon Jairo Osorio-Méndez, Luis Alberto Gómez, Gladis Montoya-Ortiz

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 945 - 945

Опубликована: Янв. 23, 2025

Cardiovascular diseases and cancer are leading global causes of morbidity mortality, necessitating advances in diagnosis treatment. Doxorubicin (Doxo), a potent chemotherapy drug, long-term heart damage due to cardiotoxicity. Small extracellular vesicles (sEVs) carry bioactive molecules—such as proteins, lipids, nucleic acids—that can modulate gene expression signaling pathways recipient cells, including cardiomyocytes. Through the delivery cytokines, microRNAs, growth factors, sEVs influence cell survival, which plays critical role development This study investigates derived from breast cells treated or not with Doxo their potential induce cardiomyocyte damage, thereby contributing We isolated MCF-7 using ultracentrifugation characterized them through Nanoparticle Tracking Analysis (NTA), Scanning Electron Microscopy (SEM), Western Blotting (WB) for markers CD63, CD81, TSG101. analyzed cytokine profiles Multiplex Assay Cytokine Membrane Array. exposed Guinea pig cardiomyocytes different concentrations sEVs. assessed viability (MTT assay), shortening, reactive oxygen species (ROS–DHE dye) production, mitochondrial membrane (JC-1 dye), calcium dynamics (FLUO-4 dye). performed statistical analyses, t-tests, ANOVA, Cohen’s d, η2 validate robustness results. Treatment 0.01 μM resulted increased particularly after 48 h exposure (~1.79 × 108 ± 2.77 107 vs. ~5.1 1.28 particles/mL, n = 3, p 0.0019). These exhibited protein 130–25 kDa range 93–123 nm sizes. They carried cytokines TNF-α, IL-1β, IL-4, IFN-γ, IL-10. Exposure (0.025 μg/mL 2.5 μg/mL) both Doxo-treated untreated significantly reduced viability, shortened length by up 20%, ROS disrupted homeostasis potential, indicating severe cellular stress findings suggest that enhances production key cardiotoxicity cargo. The highlights these biomarkers early detection therapeutic targets mitigate cardiovascular risks patients. Future research should focus on understanding mechanisms Doxorubicin-induced contribute exploring diagnostic improve patient safety outcomes therapy.

Язык: Английский

Процитировано

0

Effects of Hydrogels on Mesenchymal Stem/Stromal Cells Paracrine Activity and Extracellular Vesicles Production DOI Creative Commons

Oscar Fabian García‐Aponte,

Simon Kahlenberg,

Dimitrios Kouroupis

и другие.

Journal of Extracellular Vesicles, Год журнала: 2025, Номер 14(3)

Опубликована: Март 1, 2025

ABSTRACT Mesenchymal stem/stromal cells (MSCs) are a valuable source of paracrine factors, as they have remarkable secretory capacity, and there is sizeable knowledge base to develop industrial clinical production protocols. Promising cell‐free approaches for tissue regeneration immunomodulation driving research towards secretome applications, among which extracellular vesicles (EVs) steadily gaining attention. However, the manufacturing application EVs limited by insufficient yields, gaps, low standardization. Facing these limitations, hydrogels represent versatile three‐dimensional (3D) culture platform that can incorporate matrix (ECM) components mimic natural stem cell environment in vitro; via niche‐mimicking properties, regulate MSCs’ morphology, adhesion, proliferation, differentiation secretion capacities. impact hydrogel's architectural, biochemical biomechanical properties on remains poorly understood, field still its infancy interdependency parameters compromises comparability studies. Therefore, this review summarizes discusses reported effects hydrogel encapsulation MSC‐EVs. Considering cell‐material interactions overall activity MSCs, we identify persistent challenges from standardization process control, outline future paths research, such synergic use bioreactors enhance MSC‐EV generation.

Язык: Английский

Процитировано

0

Continuous collection of human mesenchymal-stromal-cell-derived extracellular vesicles from a stirred tank reactor operated under xenogeneic-free conditions for therapeutic applications DOI Creative Commons
Cristiana Ulpiano, William O.S. Salvador, Teresa Franchi-Mendes

и другие.

Stem Cell Research & Therapy, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 24, 2025

Язык: Английский

Процитировано

0

Mapping the microcarrier design pathway to modernise clinical mesenchymal stromal cell expansion DOI
Gretel Major, Vinh Khanh Doan, Alessia Longoni

и другие.

Trends in biotechnology, Год журнала: 2024, Номер 42(7), С. 859 - 876

Опубликована: Фев. 5, 2024

Язык: Английский

Процитировано

3

Generating suspension-adapted human mesenchymal stromal cells (S-hMSCs) for the scalable manufacture of extracellular vesicles DOI Creative Commons
Pedro Silva Couto,

Dale J. Stibbs,

Braulio Carrillo Sanchez

и другие.

Cytotherapy, Год журнала: 2024, Номер 26(12), С. 1532 - 1546

Опубликована: Июль 3, 2024

Human mesenchymal stromal cells (hMSCs) are a naturally adherent cell type and one of the most studied cellular agents used in therapy over last 20 years. Their mechanism action has been primarily associated with paracrine signalling, which contributed to an increase number studies focused on hMSC-related extracellular vesicles (EVs). In this study, we demonstrate for first time that human telomerase reverse transcriptase (hTERT) immortalised hMSCs can be adapted suspension culture, eliminating need microcarriers or other matrixes support growth. This novel line, named (S-hMSCs), doubling approximately 55 hours, growth rate 0.423 d−1. Regarding its immunophenotype characteristics, S-hMSCs retained close 90% CD73 CD105 expression levels, CD90 receptor being downregulated during adaptation process. An RNA sequencing analysis showed upregulation transcripts coding CD44, CD46 CD47 compared levels AT-hMSCs hTERT-hMSCs. The line herein established was able generate EVs using chemically defined medium formulation these nanoparticles averaging 150 nm size displaying markers CD63, CD81, TSG101, while not expressing negative marker calnexin. body evidence, combined visual confirmation EV presence transmission electron microscopy, demonstrates EV-producing capabilities S-hMSCs. provides platform process development, drug discovery translational field.

Язык: Английский

Процитировано

2