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

Vagif Ali oglu Gasanov,

Dmitry Kashirskikh, Victoria A. Khotina

et al.

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

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

Vagif Ali oglu Gasanov,

Dmitry Kashirskikh, Victoria A. Khotina

et al.

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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