Mesenchymal stem cell-derived extracellular vesicles in therapy against fibrotic diseases DOI Creative Commons

Yuling Huang,

Lina Yang

Stem Cell Research & Therapy, Journal Year: 2021, Volume and Issue: 12(1)

Published: Aug. 4, 2021

Abstract Fibrosis is likely to occur in many tissues and organs induce cicatrisation dysfunction. The therapeutic regimens for delaying even reversing fibrosis are quite limited at present. In nearly a decade, mesenchymal stem cells (MSCs) have been widely acknowledged as useful treating fibrotic diseases preclinical clinical trials. Further studies indicated that the effects of cell-derived extracellular vesicles (MSC-EVs) probably superior MSCs. At present, MSC-EVs attracted much attention lung, liver, kidney, skin, heart. By contrast, significant knowledge-gap remains other (including uterus, gastrointestinal tract, peritoneum) with aid MSC-EVs. This review summarises research status proposes solutions existing problems, which contribute further on treatment future.

Language: Английский

Mesenchymal stem cell-derived extracellular vesicles for immunomodulation and regeneration: a next generation therapeutic tool? DOI Creative Commons

Meng Kou,

Li Huang,

Jinjuan Yang

et al.

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(7)

Published: July 4, 2022

Mesenchymal stem cells (MSCs) can be widely isolated from various tissues including bone marrow, umbilical cord, and adipose tissue, with the potential for self-renewal multipotent differentiation. There is compelling evidence that therapeutic effect of MSCs mainly depends on their paracrine action. Extracellular vesicles (EVs) are fundamental effectors play a crucial role in intercellular communication, existing body fluids cell supernatants. Since MSC-derived EVs retain function protocells have lower immunogenicity, they wide range prospective applications advantages over therapy. We describe some characteristics MSC-EVs, discuss immune regulation regeneration, emphasis molecular mechanism application MSC-EVs treatment fibrosis support tissue repair. also highlight current challenges clinical ways to overcome problem quality heterogeneity.

Language: Английский

Citations

304
Extracellular vesicles in kidney disease DOI Open Access
Cristina Grange, Benedetta Bussolati

Nature Reviews Nephrology, Journal Year: 2022, Volume and Issue: 18(8), P. 499 - 513

Published: May 31, 2022

Language: Английский

Citations

118
Mesenchymal stem cell-derived exosomes: Characteristics and applications in disease pathology and management DOI
Hafiza Padinharayil, Jinsu Varghese, Cornelia M. Wilson

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 342, P. 122542 - 122542

Published: Feb. 28, 2024

Language: Английский

Citations

18
Histone H3K18 and Ezrin Lactylation Promote Renal Dysfunction in Sepsis‐Associated Acute Kidney Injury DOI Creative Commons
Jiao Qiao,

Yuan Tan,

Hongchao Liu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(28)

Published: May 20, 2024

Abstract Histone lactylation is a metabolic stress‐related histone modification. However, the role of in development sepsis‐associated acute kidney injury (SA‐AKI) remains unclear. Here, H3K18 (H3K18la) elevated SA‐AKI, which reported this study. Furthermore, lactate‐dependent modification enriched at promoter Ras homolog gene family member A (RhoA) and positively correlated with transcription. Correction abnormal lactate levels resulted reversal RhoA. Examination related mechanism revealed that promoted RhoA/Rho‐associated protein kinase (ROCK) /Ezrin signaling, activation nuclear factor‐κB (NF‐κB), inflammation, cell apoptosis, aggravated renal dysfunction. In addition, Ezrin can undergo Multiple sites are identified confirmed mainly occurred K263 site. The SA‐AKI reportes novel post‐translational Ezrin. Its potential regulating inflammatory adaptation proximal tubule epithelial cells also elucidated. results provide insights into epigenetic regulation onset SA‐AKI.

Language: Английский

Citations

16
Therapeutic Role of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Female Reproductive Diseases DOI Creative Commons

Zhiqi Liao,

Chang Liu, Lan Wang

et al.

Frontiers in Endocrinology, Journal Year: 2021, Volume and Issue: 12

Published: June 23, 2021

Reproductive disorders, including intrauterine adhesion (IUA), premature ovarian insufficiency (POI), and polycystic ovary syndrome (PCOS), are great threats to female reproduction. Recently, mesenchymal stem cells derived-extracellular vesicles (MSC-EVs) have presented their potentials cure these diseases, not only for the propensity ability they stemmed from parent cells, but also higher biology stability lower immunogenicity, compared MSCs. EVs lipid bilayer complexes, functional as mediators by transferring multiple molecules recipient such proteins, microRNAs, lipids, cytokines. appeared a therapeutic effect on reproductive disorder, repairing injured endometrium, suppressing fibrosis of regulating immunity anti-inflammatory, repressing apoptosis granulosa (GCs) in ovaries. Although underlying mechanisms MSC-EVs reached consensus, several theories been proposed, promoting angiogenesis, immunity, reducing oxidate stress levels. In current study, we summarized knowledge functions IUA, POI, PCOS. Given health, critical issues discussed will guide new insights this rapidly expanding field.

Language: Английский

Citations

76
Mesenchymal Stem Cell-Derived Extracellular Vesicles to the Rescue of Renal Injury DOI Open Access
Lucy Birtwistle, Xinming Chen, Carol A. Pollock

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(12), P. 6596 - 6596

Published: June 20, 2021

Acute kidney injury (AKI) and chronic disease (CKD) are rising in global prevalence cause significant morbidity for patients. Current treatments limited to slowing instead of stabilising or reversing progression. In this review, we describe mesenchymal stem cells (MSCs) their constituents, extracellular vesicles (EVs) as being a novel therapeutic CKD. MSC-derived EVs (MSC-EVs) membrane-enclosed particles, including exosomes, which carry genetic information that mimics the phenotype cell origin. MSC-EVs deliver cargo mRNA, miRNA, cytokines, growth factors target form paracrine communication. This genetically reprograms pathophysiological pathways, upregulated renal failure. Since method exosome preparation significantly affects quality function MSC-exosomes, review compares methodologies isolating exosomes from MSCs role tissue regeneration. More specifically, it summarises efficacy 60 preclinical animal models AKI CKD biomolecules they deliver. promote tubular proliferation angiogenesis, inhibit apoptosis, oxidative stress, inflammation, epithelial-to-mesenchymal transition, fibrosis, alleviate By reprogramming these can slow even reverse progression CKD, therefore offer potential transform clinical practice.

Language: Английский

Citations

65
Epithelial–mesenchymal transition in organ fibrosis development: current understanding and treatment strategies DOI Creative Commons

Lexin Liu,

Qizhe Sun,

Frank M. Davis

et al.

Burns & Trauma, Journal Year: 2022, Volume and Issue: 10

Published: Jan. 1, 2022

Abstract Organ fibrosis is a process in which cellular homeostasis disrupted and extracellular matrix excessively deposited. Fibrosis can lead to vital organ failure there are no effective treatments yet. Although epithelial–mesenchymal transition (EMT) may be one of the key mechanisms, underlying mechanisms remain largely unknown. EMT cell phenotypic epithelial cells lose their cell-to-cell adhesion polarization, after they acquire mesenchymal features such as infiltration migration ability. Upon injurious stimulation different organs, triggered by multiple signaling pathways also regulated epigenetic mechanisms. This narrative review summarizes current understanding fibrogenesis discusses potential strategies for attenuating prevent and/or inhibit fibrosis. Despite better role development, targeting beyond developing therapeutics tackle challenging but likely feasible.

Language: Английский

Citations

61
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

35
Extracellular vesicles: emerging roles, biomarkers and therapeutic strategies in fibrotic diseases DOI Creative Commons
Junyan Zhu, Sicong Wang,

Dakai Yang

et al.

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 24, 2023

Abstract Extracellular vesicles (EVs), a cluster of cell-secreted lipid bilayer nanoscale particles, universally exist in body fluids, as well cell and tissue culture supernatants. Over the past years, increasing attention have been paid to important role EVs effective intercellular communicators fibrotic diseases. Notably, EV cargos, including proteins, lipids, nucleic acids, metabolites, are reported be disease-specific can even contribute fibrosis pathology. Thus, considered biomarkers for disease diagnosis prognosis. Emerging evidence shows that derived from stem/progenitor cells great prospects cell-free therapy various preclinical models diseases engineered improve targeting effectiveness their treatment. In this review, we will focus on biological functions mechanisms diseases, potential novel therapeutic strategies.

Language: Английский

Citations

30
Milk fat globule-epidermal growth factor 8 (MFGE8) prevents intestinal fibrosis DOI
Sinan Lin, Jie Wang, Pranab K. Mukherjee

et al.

Gut, Journal Year: 2024, Volume and Issue: 73(7), P. 1110 - 1123

Published: Feb. 20, 2024

Objective Intestinal fibrosis is considered an inevitable consequence of chronic IBD, leading to stricture formation and need for surgery. During the process fibrogenesis, extracellular matrix (ECM) components critically regulate function mesenchymal cells. We characterised composition ECM in fibrostenosing Crohn’s disease (CD) control tissues. Design Decellularised full-thickness intestinal tissue platforms were tested using three different protocols, phenotypes was explored by proteomics validated quantitative PCR (qPCR) immunohistochemistry. Primary human myofibroblasts (HIMFs) treated with milk fat globule-epidermal growth factor 8 (MFGE8) evaluated regarding mechanism their antifibrotic response, action MFGE8 two experimental models. Results established optimal decellularisation protocol IBD Matrisome analysis revealed elevated expression CD strictured (CDs) tissue, which confirmed at mRNA protein levels. Treatment inhibited production normal HIMF but not CDs HIMF. Next-generation sequencing uncovered functionally relevant integrin-mediated signalling pathways, blockade integrin αvβ5 focal adhesion kinase rendered non-responsive MFGE8. prevented reversed vitro vivo. Conclusion displays effects, its administration may represent a future approach prevention IBD-induced strictures.

Language: Английский

Citations

11