Preclinical Evaluation of the Safety, Toxicity and Efficacy of Genetically Modified Wharton’s Jelly Mesenchymal Stem/Stromal Cells Expressing the Antimicrobial Peptide SE-33

Cells, Journal Year: 2025, Volume and Issue: 14(5), P. 341 - 341

Published: Feb. 26, 2025

Mesenchymal stem/stromal cells (MSCs) offer promising therapeutic potential in cell-based therapies for various diseases. However, the safety of genetically modified MSCs remains poorly understood. This study aimed to evaluate general toxicity and Wharton's Jelly-Derived (WJ-MSCs) engineered express antimicrobial peptide SE-33 an animal model. Genetically WJ-MSCs expressing were administered C57BL/6 mice at both excessive doses, either once or repeatedly. Animal monitoring included mortality, clinical signs, behavioral observations. The assessment involved histopathological, hematological, biochemical analyses major organs tissues, while immunotoxicity immunogenicity examined through humoral cellular immune responses, macrophage phagocytic activity, lymphocyte blast transformation. Antimicrobial efficacy was evaluated a Staphylococcus aureus-induced pneumonia model by mortality assessing bacterial load inflammatory processes lungs. Mice receiving exhibited no acute chronic toxicity, abnormalities, pathological changes, regardless dose administration frequency. No significant alterations responses observed, there notable changes hematological serum parameters. Infected animals treated with WJ-MSC-SE33 showed reduction lung inflammation improved survival compared control groups, demonstrating over native WJ-MSCs. Our findings suggest that are well tolerated, displaying favorable profile comparable potent significantly reducing load, inflammation, S. aureus These data support as candidate infections, particularly those complicated antibiotic resistance.

Language: Английский

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Mesenchymal Stem Cells Loaded in Injectable Alginate Hydrogels Promote Liver Growth and Attenuate Liver Fibrosis in Cirrhotic Rats

Gels, Journal Year: 2025, Volume and Issue: 11(4), P. 250 - 250

Published: March 27, 2025

Cirrhosis, a marker of severe liver diseases, limits future remnant (FLR) growth, preventing many cancer patients from undergoing surgery. While portal vein blockade (PVB) techniques are used to stimulate regeneration, 20-30% still fail achieve the required growth. Although mesenchymal stem cell (MSC) therapy improves PVB, its efficacy is limited by poor retention. To address this, we utilized alginate hydrogels deliver MSCs and improve their were loaded in hydrogel injected intraportally cirrhotic rats. Liver volume, weights, enzyme levels, histology monitored. Results showed that maintained 89.0 ± 3.0% viability gradually released for over two weeks. Furthermore, rats with MSC-loaded demonstrated higher volumes (FLR ratio 0.57 0.32) weights 0.84 0.05). The treated exhibited more improved enzymes (AST: 72.75 14.17 U/L, ALP: 135.67 41.20 ALT: 46.00 2.94 U/L) decreased fibrotic areas (4.52 0.22%) compared control group. Histology revealed increased retention when delivered (37.30 16.10 MSCs/mm2) cells alone (21.70 22.10 MSCs/mm2). Overall, enhanced growth reduced fibrosis promoting This approach holds significant potential improving outcomes among patients, offering promising therapeutic strategy regeneration treatment diseases.

Language: Английский

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Embryonic lethal abnormal vision like 1-stabilized histone deacetylase 6 promotes hepatic stellate cell activation to accelerate liver fibrosis progression through ribosomal protein S5 downregulation

CytoJournal, Journal Year: 2025, Volume and Issue: 22, P. 30 - 30

Published: March 6, 2025

Histone deacetylase 6 (HDAC6) has been confirmed to participate in the regulation of liver fibrosis (LF) progression. This study aims explore role and mechanism HDAC6 LF process. Serum samples were collected from cirrhosis (LC) patients normal healthy individuals. Human hepatic stellate cells (HSC; LX-2) stimulated with transforming growth factor β1 (TGF-β1) mimic cell models. The levels HDAC6, ribosomal protein S5 (RPS5), embryonic lethal abnormal vision like 1 (ELAVL1), fibrosis-related markers determined by quantitative real-time polymerase chain reaction or western blot. Cell proliferation invasion detected using counting kit 8 assay, 5-ethynyl-2'-deoxyuridine Transwell assay. contents inflammatory factors examined enzyme-linked immunosorbent Furthermore, co-immunoprecipitation RNA immunoprecipitation assays performed assess interaction between RPS5 ELAVL1. effect ELAVL1 knockdown on mRNA stability was evaluated Actinomycin D treatment showed increased expression LC patients. reduced TGF-β1-induced LX-2 proliferation, invasion, fibrosis, inflammation. Moreover, acetylation RPS5, reversed inhibition si-HDAC6 Meanwhile, interacted stabilize its mRNA, thus inhibiting expression. Our data revealed that ELAVL1-stabilized promoted HSC activation repressing acetylation, providing a novel target for alleviating

Language: Английский

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Efficacy Evaluation of Gardenia Fructus and Uncaria rhynchophylla Mixture in Liver-Fibrosis Models

Journal of the Korean Society of Food Science and Nutrition, Journal Year: 2024, Volume and Issue: 53(10), P. 992 - 1006

Published: Oct. 31, 2024

Hui Yeon An, Tae Jong Lee, Mi-Rae Shin, Jeong Won Choi, Min Ju Kim, Il-Ha Jeong, JiWon Jung, and Seong-Soo Roh. Journal of the Korean Society Food Science Nutrition 2024;53:992-1006. https://doi.org/10.3746/jkfn.2024.53.10.992

Language: Английский

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Hepatic encephalopathy: experimental drugs in development and therapeutic potential

Expert Opinion on Investigational Drugs, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 12

Published: Nov. 26, 2024

Hepatic encephalopathy (HE) presents a complex pathophysiology, creating multiple potential treatment avenues. This review covers current and emerging treatments for HE.

Language: Английский

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