Advances in Mesenchymal Stem Cell Therapy and Natural Antioxidants for Hepatic Fibrosis: A Comprehensive Review DOI
Abeer Kazmi, Tahira Sultana

Deleted Journal, Journal Year: 2024, Volume and Issue: 2, P. 100016 - 100016

Published: March 1, 2024

Liver damage resulting from the administration of various allopathic drugs and their associated toxicity has become a major health problem, leading to hepatic fibrosis, cirrhosis, metabolic disorders. This epidemic condition liver disease represents global cause death morbidity. Although orthotopic transplantation remains vital treatment option for fibrotic conditions, its efficacy is limited by organ scarcity risk immunological rejection. Consequently, alternative therapeutic approaches are urgently needed. Cell-based therapy utilizing mesenchymal stem cells (MSCs) garnered considerable interest as promising modality. MSCs exhibit immunomodulatory properties can differentiate into hepatocytes, thus facilitating regeneration damaged hepatocytes increasing residual hepatocyte proliferation while inhibiting activation or apoptosis stellate cells. However, despite potential benefits, transplanted often low survival rates due inadequate oxidative inflammatory stress resistance. Plants harbor diverse array bioactive compounds known possess hepatoprotective antioxidant properties. Nanomaterials play crucial role in regenerative medicine providing targeted delivery agents scaffolds tissue engineering. In treating liver, nanomaterials help mitigate fibrosis progression promote through controlled release anti-fibrotic growth factors. review highlights synergistic cell-based therapy, natural antioxidants, differentiation factors, nanotechnology combating advancing medicine. These combined offer avenues effectively conditions promoting regeneration.

Language: Английский

One-step engineered mesenchymal stem cell-derived exosomes against hepatic ischemia–reperfusion injury DOI

Xinfeng Lu,

Haitao Hu, Yujie Zhou

et al.

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown, P. 125292 - 125292

Published: Jan. 1, 2025

Language: Английский

Citations

0
Engineered extracellular vesicles: an emerging nanomedicine therapeutic platform DOI

Jingshi Tang,

Dezhong Li, Rui Wang

et al.

Chemical Communications, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Extracellular vesicles have been deemed as potential drug carriers for treatment of various diseases. Recent advances summarized, including the sources, delivery function, extraction and cargo-loading technology extracellular vesicles.

Language: Английский

Citations

0
Mesenchymal stem cell-derived small extracellular vesicles reduced hepatic lipid accumulation in MASLD by suppressing mitochondrial fission DOI Creative Commons
Yifei Chen,

Fuji Yang,

Yanjin Wang

et al.

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 5, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic characterized by lipid accumulation in cells. Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) have great potential repairing and regenerating diseases. However, it still unclear whether MSC-sEV can inhibit hepatocyte regulating mitochondrial fission. We investigated the effects of on fission its mechanism lipotoxic hepatocytes high-fat diet (HFD)-induced MASLD mice. found that effectively expression Dynamin-related protein 1 (DRP1), thereby reducing fission, damage, deposition livers HFD-induced Further mechanistic studies revealed RING finger 31 (RNF31) played crucial role mediating inhibitory effect DRP1 RNF31 suppress improving dysfunction deposition. These findings suggest may downregulate DRP1-mediated transporting RNF31, ultimately inhibiting accumulation. The insights from this study provide new perspective offer therapeutic target targeting to steatosis progression MASLD.

Language: Английский

Citations

0
Exosomal miR-499a-5p from human umbilical cord mesenchymal stem cells attenuates liver fibrosis via targeting ETS1/GPX4-mediated ferroptosis in hepatic stellate cells DOI Creative Commons
Zheng Wang, Mengqin Yuan, Lichao Yao

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 19, 2025

Liver fibrosis is a leading cause of liver-related mortality worldwide, yet effective therapies remain limited. Mesenchymal stem cells (MSCs) have recently shown promise in treating liver due to their anti-inflammatory and anti-fibrotic properties. However, the precise molecular mechanisms by which MSCs exert effects unclear. In this study, we explored how human umbilical cord-derived mesenchymal (hUC-MSCs) contribute fibrosis, revealed crucial role ferroptosis modulating hepatic stellate (HSCs) activity. We found that primarily promote HSCs an exosome-dependent manner. Specifically, MSC-derived exosomes (MSC-Exos) deliver miR-499a-5p, interacts with transcription factor ETS1, suppression GPX4, key regulator ferroptosis, thereby reducing fibrogenic activity HSCs. Overexpression ETS1 counteracted miR-499a-5p-induced underscoring pathway's potential as target for therapeutic intervention. Furthermore, docking simulations further identified optimal ETS1-GPX4 binding sites. This research uncovers novel mechanism may treat providing insights could guide development more widespread condition.

Language: Английский

Citations

0
Engineered ATP-Loaded Extracellular Vesicles Derived from Mesenchymal Stromal Cells: A Novel Strategy to Counteract Cell ATP Depletion in an In Vitro Model DOI Open Access
Maria Antonietta Grignano, Silvia Pisani, Marilena Gregorini

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3424 - 3424

Published: April 5, 2025

The use of adenosine triphosphate (ATP) has shown promising effects in alleviating ischemic damage across various tissues. However, the penetration ATP into kidney tubular cells presents a challenge due to their unique anatomical and physiological properties. In this study, we introduce novel bioinspired drug delivery system utilizing extracellular vesicles (EVs) derived from mesenchymal stromal (MSCs) engineered carry ATP. ATP-loaded liposomes (ATP-LPs) EVs (ATP-EVs) were prepared using microfluidic technology, followed by characterization morphology (DLS, NTA, SEM, TEM), content, release rate at 37 °C (pH 7.4). Additionally, efficacy ATP-LPs ATP-EVs was evaluated vitro on renal (HK2 cells) under chemically induced ischemia. results indicated successful enrichment EVs, with showing no significant changes or size compared naïve EVs. Notably, demonstrated superior retention ATP-LPs, protecting degradation environment. an ATP-depleted HK2 cell model, only effectively restored levels, preserving viability reducing apoptotic gene expression (BCL2-BAX). This study is first successfully demonstrate direct as carriers.

Language: Английский

Citations

0
G-LERP/miR-374i-b Attenuates IRI and Suppresses Hepatocellular Carcinoma Progression DOI

Chang Xie,

Nasha Qiu, Chao Wang

et al.

Transplantation, Journal Year: 2025, Volume and Issue: unknown

Published: May 8, 2025

Background. Liver transplantation (LT) is the most effective therapeutic strategy for late-stage hepatocellular carcinoma (HCC), but it prone to ischemia–reperfusion injury (IRI), leading poor prognosis. Previous articles have reported that miR-374b-5p expression increased in HCC tissues, and its relationship with IRI progression unclear. Methods. reports shown significantly upregulated tissues. The effect of on patient symptoms prognosis were analyzed from Cancer Genome Atlas database liver specimens LT patients. To further explore potential, a liver-targeted esterase-responsive gene delivery system (G-LERP/miR-374i-b) was developed downregulate mouse hepatic (HIRI) model. An orthotopic model established mimic postoperative recurrence HCC. Results. In this study, we found correlates tumor size microvascular invasion based patients’ clinical information. Patients low had higher Milan criteria score lower Model End-stage Disease score. We verified positive correlation between proliferation cells. Effective downregulation simultaneously alleviated HIRI reduced burden by 56%, whereas upregulation promoted progression. Furthermore, G-LERP/miR-374i-b attenuated inflammation downregulating nuclear factor kappa-B pathway, thereby reducing risk recurrence. Conclusions. This research first demonstrate as dual target during Preintervention using an preoperative period alleviates suppresses

Language: Английский

Citations

0
An Esterase-Responsive SLC7A11 shRNA Delivery System Induced Ferroptosis and Suppressed Hepatocellular Carcinoma Progression DOI Creative Commons
Hui Zhang, Jianguo Wang, Xiaonan Xiang

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(2), P. 249 - 249

Published: Feb. 8, 2024

Ferroptosis has garnered attention as a potential approach to fight against cancer, which is characterized by the iron-driven buildup of lipid peroxidation. However, robust defense mechanisms intracellular ferroptosis pose significant challenges its effective induction. In this paper, an gene delivery vehicle was developed transport solute carrier family 7 member 11 (SLC7A11) shRNA (shSLC7A11), downregulates expression channel protein SLC7A11 and glutathione peroxidase 4 (GPX4), evoking surge in reactive oxygen species production, iron accumulation, peroxidation hepatocellular carcinoma (HCC) cells, subsequently leading ferroptosis. This system composed HCC-targeting layer esterase-responsive cationic polymer, poly{N-[2-(acryloyloxy)ethyl]-N-[p-acetyloxyphenyl]-N} (PQDEA) condensed shSLC7A11 core (G−LPQDEA/shSLC7A11). After intravenous (i.v.) injection, G−LPQDEA/shSLC7A11 quickly accumulated tumor, retarding growth 77% improving survival two times. study first construct system, G−LPQDEA/shSLC7A11, that effectively inhibits HCC progression downregulating expression. underscores therapeutic safe valuable candidate for clinical treatment.

Language: Английский

Citations

3
Mesenchymal stem cell therapy for liver transplantation: clinical progress and immunomodulatory properties DOI Creative Commons

Fuli Wen,

Guokai Yang,

Saihua Yu

et al.

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 27, 2024

Language: Английский

Citations

2
Mesenchymal Stem Cells Prevent SLC39A14‐Dependent Hepatocyte Ferroptosis through Exosomal miR‐16‐5p in Liver Graft DOI Creative Commons

Zhizhao Deng,

Weiqi Zeng,

Yingxin Gao

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract Ischemia‐reperfusion injury (IRI) is the leading cause of hepatic graft dysfunction, resulting from hepatocyte damage. Nevertheless, given few specialized therapeutics available in IRI, additional mechanistic insights into damage are required. Here, protein solute carrier family 39 member 14 (SLC39A14) identified as a pro‐ferroptosis target hepatocytes human liver allografts through single‐cell RNA sequencing analysis. SLC39A14 knockdown significantly mitigated IRI by preventing ferroptosis vivo and vitro. Mechanistically, inhibition suppressed non‐transferrin‐bound iron (NTBI) uptake hepatocytes, thereby reducing overload cell ferroptosis. Moreover, bone marrow‐derived mesenchymal stem cells (hBMSCs) found to exhibit notable therapeutic effect on downregulating expression. Exosomes derived hBMSCs delivered abundant miR‐16‐5p which post‐transcriptionally expression reduced induced IRI. In conclusion, triggers mediating NTBI inducing hBMSC‐based therapy promising reverse this progression

Language: Английский

Citations

2
Native and engineered extracellular vesicles: novel tools for treating liver disease DOI

Shuangshuang Jiang,

Siyuan Tian,

Punan Wang

et al.

Journal of Materials Chemistry B, Journal Year: 2024, Volume and Issue: 12(16), P. 3840 - 3856

Published: Jan. 1, 2024

Liver diseases are classified as acute liver damage and chronic disease, with recurring causing fibrosis progression to cirrhosis hepatoma. transplantation is the only effective treatment for end-stage diseases; therefore, novel therapies required. Extracellular vesicles (EVs) endogenous nanocarriers involved in cell-to-cell communication that play important roles immune regulation, tissue repair regeneration. Native EVs can potentially be used various owing their high biocompatibility, low immunogenicity permeability engineered surface modification or cargo loading could further optimize therapeutic effects. In this review, we firstly introduced mechanisms effects of native derived from different cells tissues treat etiologies. Additionally, summarized possible methods facilitate targeting improve cargo-loading efficiency. detailed latest delivery strategies were also discussed. Finally, pointed out limitations challenges future development applications. We hope review provide a useful reference promote clinical translation.

Language: Английский

Citations

1