S‐Nitrosylation of NOTCH1 Regulates Mesenchymal Stem Cells Differentiation Into Hepatocyte‐Like Cells by Inhibiting Notch Signalling Pathway DOI Creative Commons

Xuesong Wang,

Yan Xu, Yue Wang

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(23)

Published: Dec. 1, 2024

The differentiation of mesenchymal stem cells (MSCs) into hepatocyte-like (HLCs) is considered one the most promising strategies for alternative hepatocyte transplantation to treat end-stage liver disease. To advance this method, it crucial gain a deeper understanding mechanisms governing hepatogenic differentiation. study demonstrated that suppression intracellular domain release Notch pathway receptor via γ-secretase inhibitor N-[(3, 5-difluorophenyl)acetyl]-L-alanyl-2-phenylglycine-1, 1-dimethylethyl ester (DAPT) significantly promotes expression hepatocyte-related genes and proteins in HLCs. Increased inducible NO synthase (iNOS) during led elevated endogenous production. Biotin switch assays revealed gradual increase S-nitrosylation (SNO)-NOTCH1 decrease overall NOTCH1 addition exogenous donor S-nitrosoglutathione (GSNO) SNO dithiothreitol (DTT) further SNO-NOTCH1 MSCs mature hepatocytes. Briefly, our results fully modification extracellular by NO, leading formation SNO-NOTCH1, inhibiting signalling pathway. Our highlights critical role regulating offers new insights driving process.

Language: Английский

Enhancing mesenchymal stem cell survival and homing capability to improve cell engraftment efficacy for liver diseases DOI Creative Commons
Shaoxiong Yu,

Saihua Yu,

Haiyan Liu

et al.

Stem Cell Research & Therapy, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 4, 2023

Abstract Although mesenchymal stem cell (MSC) transplantation provides an alternative strategy for end-stage liver disease (ESLD), further widespread application of MSC therapy is limited owing to low engraftment efficiency. Improving efficiency plays a critical role in enhancing diseases. In this review, we summarize the current status and challenges ESLD. We also outline complicated cell-homing process highlight how closely related huge differences extracellular conditions involved homing journeys ranging from constant, controlled vitro variable challenging vivo. survival capabilities enhances efficacy. Therefore, strategies, including hypoxic priming, drug pretreatment, gene modification, cytokine as well splenectomy local irradiation, used improve capability, enhance therapeutic therapy. hope that review will provide new insights into

Language: Английский

Citations

29

Emerging advanced approaches for diagnosis and inhibition of liver fibrogenesis DOI Creative Commons

Tamer A. Addissouky,

Majeed M. A. Ali, Ibrahim El Tantawy El Sayed

et al.

The Egyptian Journal of Internal Medicine, Journal Year: 2024, Volume and Issue: 36(1)

Published: Feb. 12, 2024

Abstract Background Liver fibrosis results from chronic liver injury and is characterized by excessive deposition of extracellular matrix proteins including collagen. It can progress to cirrhosis failure. Main body the abstract Multiple cellular signaling pathways drive hepatic stellate cell activation fibrogenesis. Advances in biomarkers, imaging modalities, omics platforms enable noninvasive diagnosis staging fibrosis. Emerging antifibrotic approaches include medications like pirfenidone, obeticholic acid, monoclonal antibodies targeting pro-fibrotic mediators. Cell therapies using mesenchymal stem cells demonstrate potential through paracrine immunosuppression. Tissue-engineered grafts biomaterial carriers for localized drug delivery are promising technologies. Microfluidic liver-on-a-chip with patient-derived provide unprecedented models study human test candidates. Short conclusion Significant has elucidated mechanisms underlying fibrogenesis uncovered novel therapeutic targets. Ongoing challenges translating preclinical findings, improving efficacy, enabling personalized precision medicine approaches. Further research into combinatorial therapies, tissue engineering technologies will advance treatment all causes.

Language: Английский

Citations

9

Old age as a risk factor for liver diseases: Modern therapeutic approaches DOI Creative Commons
Milena Georgieva, Charilaos Xenodochidis, Natalia Krasteva

et al.

Experimental Gerontology, Journal Year: 2023, Volume and Issue: 184, P. 112334 - 112334

Published: Nov. 25, 2023

Recent scientific interest has been directed towards age-related diseases, driven by the significant increase in global life expectancy and growing population of individuals aged 65 above. The ageing process encompasses various biological, physiological, environmental, psychological, behavioural, social changes, leading to an augmented susceptibility chronic illnesses. Cardiovascular, neurological, musculoskeletal, liver oncological diseases are prevalent elderly. Moreover, demonstrate reduced regenerative capacity decreased tolerance therapeutic interventions, including organ transplantation. Liver such as non-alcoholic fatty disease, alcoholic hepatitis, fibrosis, cirrhosis, have emerged public health concerns. Paradoxically, these conditions remain underestimated despite their substantial impact. Age-related factors closely associated with severity unfavorable prognosis warranting further investigation enhance clinical management develop novel strategies. This comprehensive review focuses specifically on treatment strategies, contemporary practices. It provides a detailed account burden, types, molecular mechanisms, epigenetic alterations underlying pathologies.

Language: Английский

Citations

13

Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics DOI Creative Commons
Xiao Ma, Tengda Huang, Xi Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 8, 2025

Language: Английский

Citations

0

Human Umbilical Cord-Derived Mesenchymal Stem Cells Attenuate Liver Fibrosis by Inhibiting Hepatocyte Ferroptosis Through Mitochondrial Transfer DOI Creative Commons

Zhiyu Xiong,

Ping Chen, Zheng Wang

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: 231, P. 163 - 177

Published: Feb. 27, 2025

Language: Английский

Citations

0

Cell therapy for liver disorders: past, present and future DOI
María del Carmen Ortuño‐Costela, Massimo Pinzani, Ludovic Vallier

et al.

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Language: Английский

Citations

0

Extracellular vesicles targeting non-parenchymal cells: the therapeutical effect on liver fibrosis DOI Creative Commons

Yingying Liu,

Lin Wang

eGastroenterology, Journal Year: 2024, Volume and Issue: 2(1), P. e100040 - e100040

Published: March 1, 2024

Liver fibrosis is the formation of a fibrous scar due to chronic liver disease including viral hepatitis, alcohol and non-alcoholic fatty disease. Without treatment, it will develop into cirrhosis hepatocellular carcinoma. Up now, there no effective way cure fibrosis. Extracellular vesicles (EVs) are biological nanoparticles with potential be therapeutical agents or delivery tools. A lot studies have demonstrated effect EVs on In this review, we mainly pay attention roles non-parenchymal cells in pathology fibrosis, basic information about when they act cells.

Language: Английский

Citations

3

Strategies to improve the therapeutic efficacy of mesenchymal stem cell‐derived extracellular vesicle (MSC-EV): a promising cell-free therapy for liver disease DOI Creative Commons
Lijuan Zheng, Hui Gong, Jing Zhang

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2023, Volume and Issue: 11

Published: Dec. 13, 2023

Liver disease has emerged as a significant worldwide health challenge due to its diverse causative factors and therapeutic complexities. The majority of liver diseases ultimately progress end-stage transplantation remains the only effective therapy with limitations donor organ shortage, lifelong immunosuppressants expensive treatment costs. Numerous pre-clinical studies have revealed that extracellular vesicles released by mesenchymal stem cells (MSC-EV) exhibited considerable potential in treating diseases. Although natural MSC-EV many advantages, some characteristics MSC-EV, such heterogeneity, uneven effect, rapid clearance vivo constrain clinical translation. In recent years, researchers explored plenty ways improve efficacy rotation rate disease. this review, we summarized current strategies enhance potency mainly including optimization culture conditions MSC or modifications aiming facilitate development application

Language: Английский

Citations

8

Isolation, culture, and delivery considerations for the use of mesenchymal stem cells in potential therapies for acute liver failure DOI Creative Commons
Hui Yang, Jiaxian Chen, ­Jun Li­

et al.

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

Published: Sept. 7, 2023

Acute liver failure (ALF) is a high-mortality syndrome for which transplantation considered the only effective treatment option. A shortage of donor organs, high costs and surgical complications associated with immune rejection constrain therapeutic effects transplantation. Recently, mesenchymal stem cell (MSC) therapy was recognized as an alternative strategy Bone marrow cells (BMSCs) have been used in clinical trials several diseases due to their ease acquisition, strong proliferation ability, multipotent differentiation, homing lesion site, low immunogenicity anti-inflammatory antifibrotic effects. In this review, we comprehensively summarized harvest culture expansion strategies BMSCs, development animal models ALF different aetiologies, critical mechanisms BMSC challenge application.

Language: Английский

Citations

5

Biodistribution and Safety of Human Multi-Chimeric Cells After Systemic Intraosseous and Intravenous Administration in the Experimental Mouse Model DOI
Maria Siemionow, Lucile Chambily, Joanna Cwykiel

et al.

Stem Cells and Development, Journal Year: 2024, Volume and Issue: 33(9-10), P. 214 - 227

Published: March 6, 2024

Cellular therapies provide promising options for inducing tolerance in transplantation of solid organs, bone marrow, and vascularized composite allografts. However, novel tolerance-inducing protocols remain limited, despite extensive research. We previously introduced characterized a human multi-chimeric cell (HMCC) line, created through ex vivo fusion umbilical cord blood (UCB) cells derived from three unrelated donors. In this study, we assessed biodistribution safety HMCCs the NOD.Cg-Prkdc

Language: Английский

Citations

1