Gasanov Vagif Ali Oglu, Kashirskikh Dmitry Alexandrovich, Khotina Victoria Alexandrovna, Lee Arthur Anatolievich, Nikitochkina Sofya Yurievna, Kuzmina Daria Mikhailovna, Mukhina Irina Vasilievna, Vorotelyak Ekaterina Andreevna, Vasiliev Andrey Valentinovich
Koltzov Institute of Developmental Biology of Russian Academy of Sciences, Moscow 119334, Russia.
Department of Normal Physiology, Privolzhsky Research Medical University of Ministry of Health of the Russian Federation, Nizhny Novgorod 603005, Russia.
Antibiotics (Basel). 2025 Apr 24;14(5):429. doi: 10.3390/antibiotics14050429.
The genetic modification of mesenchymal stromal/stem cells (MSCs) to express antimicrobial peptides may provide a promising strategy for developing advanced cell-based therapies for 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 antimicrobial peptide SE-33 (WJ-MSC-SE33) effectively reduce bacterial load, inflammation, and mortality in a mouse model of -induced pneumonia compared with native WJ-MSCs. The present study aimed to evaluate the pharmacokinetics and tissue distribution of the SE-33 peptide expressed by WJ-MSC-SE33 following administration to animals.
WJ-MSC-SE33 were administered to C57BL/6 mice at therapeutic and excess doses. The biodistribution and pharmacokinetics of the SE-33 peptide were analyzed in serum, lungs, liver, and spleen using chromatographic methods after single and repeated administrations.
The SE-33 peptide exhibited dose-dependent pharmacokinetics. The highest levels of SE-33 peptide were detected in the liver and lungs, with persistence in tissues for up to 48 h at medium and high doses of administered WJ-MSC-SE33. A repeated administration of WJ-MSC-SE33 increased SE-33 levels in target organs.
The SE-33 peptide expressed by genetically modified WJ-MSCs demonstrated predictable pharmacokinetics and effective biodistribution. These findings, together with the previously established safety profile of WJ-MSC-SE33, support its potential as a promising cell-based therapy for bacterial infections, particularly those associated with antibiotic resistance.
对间充质基质/干细胞（MSCs）进行基因改造以表达抗菌肽，可能为开发针对细菌感染（包括由耐抗生素细菌引起或并发的感染）的先进细胞疗法提供一种有前景的策略。我们之前已经证明，与天然的沃顿胶衍生间充质干细胞相比，表达抗菌肽SE-33的基因改造沃顿胶衍生间充质干细胞（WJ-MSC-SE33）能有效降低小鼠诱导性肺炎模型中的细菌载量、炎症和死亡率。本研究旨在评估WJ-MSC-SE33给药后所表达的SE-33肽在动物体内的药代动力学和组织分布。
以治疗剂量和过量剂量将WJ-MSC-SE33给予C57BL/6小鼠。在单次和重复给药后，使用色谱方法分析血清、肺、肝和脾中SE-33肽的生物分布和药代动力学。
SE-33肽表现出剂量依赖性药代动力学。在肝和肺中检测到的SE-33肽水平最高，在中等和高剂量的WJ-MSC-SE33给药后，其在组织中的持续时间长达48小时。重复给予WJ-MSC-SE33可提高靶器官中SE-33的水平。
基因改造的WJ-MSCs所表达的SE-33肽表现出可预测的药代动力学和有效的生物分布。这些发现，连同先前确定的WJ-MSC-SE33的安全性，支持其作为一种有前景的针对细菌感染（特别是与抗生素耐药性相关的感染）的细胞疗法的潜力。
