Cellular expansion of MSCs: Shifting the regenerative potential

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

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The Potential of MSC-Based Cell-Free Therapy in Wound Healing—A Thorough Literature Review

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(11), P. 9356 - 9356

Published: May 27, 2023

A wound is an interruption of the normal anatomic structure and function skin, which critical in protecting against foreign pathogens, regulating body temperature water balance. Wound healing a complex process involving various phases, including coagulation, inflammation, angiogenesis, re-epithelialization, re-modeling. Factors such as infection, ischemia, chronic diseases diabetes can compromise healing, leading to refractory ulcers. Mesenchymal stem cells (MSCs) have been used treat models due their paracrine activity (secretome) extracellular vehicles (exosomes) that contain several molecules, long non-coding RNAs (lncRNAs), micro-RNAs (miRNAs), proteins, lipids. Studies shown MSCs-based cell-free therapy using secretome exosomes has great potential regenerative medicine compared MSCs, there are fewer safety concerns. This review provides overview pathophysiology cutaneous wounds each phase healing. It also discusses clinical studies therapies.

Language: Английский

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Emerging biomedical technologies for scarless wound healing

Bioactive Materials, Journal Year: 2024, Volume and Issue: 42, P. 449 - 477

Published: Sept. 11, 2024

Language: Английский

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Mesenchymal Stem Cell-Based Therapy as an Alternative to the Treatment of Acute Respiratory Distress Syndrome: Current Evidence and Future Perspectives

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(15), P. 7850 - 7850

Published: July 22, 2021

Acute respiratory distress syndrome (ARDS) represents a current challenge for medicine due to its incidence, morbidity and mortality and, also, the absence of an optimal treatment. The COVID-19 outbreak only increased urgent demand affordable, safe effective treatment this process. Early clinical trials suggest therapeutic usefulness mesenchymal stem cells (MSCs) in acute lung injury (ALI) ARDS. MSC-based therapies show antimicrobial, anti-inflammatory, regenerative, angiogenic, antifibrotic, anti-oxidative stress anti-apoptotic actions, which can thwart physiopathological mechanisms engaged In addition, MSC secretome their derived products, especially exosomes, may reproduce effects injury. This last strategy could avoid several safety issues potentially associated with transplantation living proliferative cell populations be formulated different forms. However, following diverse limitations must addressed: (i) selection MSC, bearing mind both heterogeneity among donors across histological origins, (ii) massive obtention these biological products through genetic manipulations most appropriate (iii) bioreactors that allow growth 3D, (iv) ideal culture conditions (v) adequate functional testing obtaining before application.

Language: Английский

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Human gingival fibroblast secretome accelerates wound healing through anti-inflammatory and pro-angiogenic mechanisms

npj Regenerative Medicine, Journal Year: 2020, Volume and Issue: 5(1)

Published: Dec. 10, 2020

Abstract Healing of the skin and oral mucosa utilises similar mechanisms tissue repair, however, scarring rate wound closure is vastly superior in cavity suggesting differences between these two environments. One key difference phenotype dermal fibroblasts compared to gingival tissues. Human (hGFs) are undifferentiated cells with multi-differentiation self-renewal capacities. This study aimed examine if delivering hGFs or their secretome, contained hGF-conditioned media (hGF-CM), would improve healing recapitulate features healing. fibroblasts, keratinocytes endothelial were first treated hGF-CM showed improved migration, proliferation angiogenic functions. A significant reduction macroscopic area histologic width, as well an increased re-epithelialisation, observed both murine excisional wounds. improvement was associated reduced inflammation, angiogenesis elevated collagen deposition. These findings demonstrate that treatment wounds either may provide beneficial gingival-like properties be a potential opportunity for improving skin.

Language: Английский

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Aging and Mesenchymal Stem Cells: Basic Concepts, Challenges and Strategies

Biology, Journal Year: 2022, Volume and Issue: 11(11), P. 1678 - 1678

Published: Nov. 18, 2022

Aging and frailty are complex processes implicating multifactorial mechanisms, such as replicative senescence, oxidative stress, mitochondrial dysfunction, or autophagy disorder. All of these mechanisms drive dramatic changes in the tissue environment, senescence-associated secretory phenotype factors inflamm-aging. Thus, there is a demand for new therapeutic strategies against devastating effects aging associated diseases. Mesenchymal stem cells (MSC) participate “galaxy” signals (proliferative, anti-inflammatory, antioxidative proangiogenic, antitumor, antifibrotic, antimicrobial effects) contributing to homeostasis. However, MSC also not immune aging. Three based on have been proposed: remove, rejuvenate, replace senescent MSC. These include use senolytic drugs, antioxidant agents genetic engineering, transplantation younger Nevertheless, may drawback adverse prolonged different drugs used or, where appropriate, those cell therapy. In this review, we propose strategy “Exogenous Restitution Intercellular Signalling Stem Cells” (ERISSC). This concept potential secretome from MSC, which composed molecules growth factors, cytokines, extracellular vesicles same biological their parent cells. To face cell-free regenerative therapy challenge, clarify key aspects, establishing tools that allow us more precise diagnosis order identify requirements adapted each case, ideal type context functional heterogeneity cellular populations, optimize mass production standardization primary materials (cells) secretome-derived products, establish appropriate methods validate anti-aging determine most route administration case.

Language: Английский

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Stem Cell-Based Therapy: A Promising Treatment for Diabetic Foot Ulcer

Biomedicines, Journal Year: 2022, Volume and Issue: 10(7), P. 1507 - 1507

Published: June 25, 2022

Diabetic foot ulcer (DFU) is a severe complication of diabetes and challenging medical condition. Conventional treatments for DFU have not been effective enough to reduce the amputation rates, which urges need additional treatment. Stem cell-based therapy has investigated over past years. Its therapeutic effect through promoting angiogenesis, secreting paracrine factors, stimulating vascular differentiation, suppressing inflammation, improving collagen deposition, immunomodulation. It controversial type origin stem cells, administration route would be most optimal therapy. We reviewed different types origins cells routes used treatment in clinical preclinical studies. Diabetes leads impairment diseased patients, makes it less ideal use autologous requires looking matching donor. Moreover, angioplasty could complementary cell therapy, scaffolds positive impact on healing process by In short, promising field regenerative medicine, but more studies are still needed determine required their safety, proper dosing, route.

Language: Английский

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Paracrine Effects of Mesenchymal Stem Cells in Ischemic Stroke: Opportunities and Challenges

Molecular Neurobiology, Journal Year: 2022, Volume and Issue: 59(10), P. 6281 - 6306

Published: Aug. 3, 2022

Language: Английский

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Mechanotransduction in Mesenchymal Stem Cells (MSCs) Differentiation: A Review

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(9), P. 4580 - 4580

Published: April 21, 2022

Mechanotransduction is the process by which physical force converted into a biochemical signal that used in development and physiology; meanwhile, it intended for ability of cells to sense respond mechanical forces activating intracellular signals transduction pathways relative phenotypic adaptation. It encompasses role stimuli developmental, morphological characteristics, biological processes different organs; response mechanically induced now also emerging as major determinant disease. Due fluid shear stress caused blood flowing tangentially across lumen surface, cardiovascular system are typically exposed variety mechanotransduction. In body, tissues continuously ranging from compression strain, pressure compressive forces. Only lately, though, has importance how shape stem cell differentiation lineage-committed can cause or exacerbate disease besides organizing been acknowledged. Mesenchymal (MSCs) potent mediators cardiac repair secret large array soluble factors have shown play huge tissue repair. Differentiation MSCs required regulate such stress, rigidity extracellular matrix through various signaling their use regenerative medicine. present review, we highlighted influences on general involved differentiation. The purpose this study demonstrate progress achieved understanding perceive react environment, well highlight areas where more research performed previous studies fill gaps.

Language: Английский

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Wharton’s jelly mesenchymal stem cells: a concise review of their secretome and prospective clinical applications

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: June 27, 2023

Accumulating evidence indicates that most primary Wharton’s jelly mesenchymal stem cells (WJ-MSCs) therapeutic potential is due to their paracrine activity, i.e., ability modulate microenvironment by releasing bioactive molecules and factors collectively known as secretome. These can either be released directly into the surrounding or embedded within membrane-bound extracellular nano-sized (usually 30–150 nm) messenger particles vesicles of endosomal origin with specific route biogenesis, exosomes carried relatively larger (100 nm–1 μm) formed outward blebbing plasma membrane called microvesicles (MVs); MVs are (EVs). The found in secretome various types, including cytokines, chemokines, cytoskeletal proteins, integrins, growth factors, angiogenic mediators, hormones, metabolites, regulatory nucleic acid molecules. As expected, performs different biological functions, such immunomodulation, tissue replenishment, cellular homeostasis, besides possessing anti-inflammatory anti-fibrotic effects. This review highlights current advances research on WJ-MSCs’ its prospective clinical applications.

Language: Английский

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