Genetically Modified Mesenchymal Stromal/Stem Cells as a Delivery Platform for SE-33, a Cathelicidin LL-37 Analogue: Preclinical Pharmacokinetics and Tissue Distribution in C57BL/6 Mice DOI Creative Commons

Vagif Ali oglu Gasanov,

Dmitry Kashirskikh, Victoria A. Khotina

et al.

Antibiotics, Journal Year: 2025, Volume and Issue: 14(5), P. 429 - 429

Published: April 24, 2025

Background: The genetic modification of mesenchymal stromal/stem cells (MSCs) to express antimicrobial peptides may provide a promising strategy for developing advanced cell-based therapies bacterial infections, including those caused or complicated by antibiotic-resistant bacteria. We have previously demonstrated that genetically modified Wharton’s jelly-derived MSCs expressing an peptide SE-33 (WJ-MSC-SE33) effectively reduce load, inflammation, and mortality in mouse model Staphylococcus aureus-induced pneumonia compared with native WJ-MSCs. present study aimed evaluate the pharmacokinetics tissue distribution expressed WJ-MSC-SE33 following administration animals. Methods: were administered C57BL/6 mice at therapeutic excess doses. biodistribution analyzed serum, lungs, liver, spleen using chromatographic methods after single repeated administrations. Results: exhibited dose-dependent pharmacokinetics. highest levels detected liver persistence tissues up 48 h medium high doses WJ-MSC-SE33. A increased target organs. Conclusions: WJ-MSCs predictable effective biodistribution. These findings, together established safety profile WJ-MSC-SE33, support its potential as therapy particularly associated antibiotic resistance.

Language: Английский

Genetically Modified Mesenchymal Stromal/Stem Cells as a Delivery Platform for SE-33, a Cathelicidin LL-37 Analogue: Preclinical Pharmacokinetics and Tissue Distribution in C57BL/6 Mice DOI Creative Commons

Vagif Ali oglu Gasanov,

Dmitry Kashirskikh, Victoria A. Khotina

et al.

Antibiotics, Journal Year: 2025, Volume and Issue: 14(5), P. 429 - 429

Published: April 24, 2025

Background: The genetic modification of mesenchymal stromal/stem cells (MSCs) to express antimicrobial peptides may provide a promising strategy for developing advanced cell-based therapies bacterial infections, including those caused or complicated by antibiotic-resistant bacteria. We have previously demonstrated that genetically modified Wharton’s jelly-derived MSCs expressing an peptide SE-33 (WJ-MSC-SE33) effectively reduce load, inflammation, and mortality in mouse model Staphylococcus aureus-induced pneumonia compared with native WJ-MSCs. present study aimed evaluate the pharmacokinetics tissue distribution expressed WJ-MSC-SE33 following administration animals. Methods: were administered C57BL/6 mice at therapeutic excess doses. biodistribution analyzed serum, lungs, liver, spleen using chromatographic methods after single repeated administrations. Results: exhibited dose-dependent pharmacokinetics. highest levels detected liver persistence tissues up 48 h medium high doses WJ-MSC-SE33. A increased target organs. Conclusions: WJ-MSCs predictable effective biodistribution. These findings, together established safety profile WJ-MSC-SE33, support its potential as therapy particularly associated antibiotic resistance.

Language: Английский

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