Comprehensive toxicity and immunogenicity studies reveal minimal effects in mice following sustained dosing of extracellular vesicles derived from HEK293T cells

Autor: Thomas D. Schmittgen, Jeffrey J. Chalmers, Ola A. Elgamal, Mohamed Badawi, Jinmai Jiang, Xiaokui Mo, Mitch A. Phelps, Alice Baek, Steven M. Pomeroy, Krista M. D. La Perle, Xiaohua Zhu, Dhruvitkumar S. Sutaria, Zhiliang Xie
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Journal of Extracellular Vesicles
Journal of Extracellular Vesicles, Vol 6, Iss 1 (2017)
ISSN: 2001-3078
Popis: Extracellular vesicles (EVs) are under evaluation as therapeutics or as vehicles for drug delivery. Preclinical studies of EVs often use mice or other animal models to assess efficacy and disposition. However, as most EVs under evaluation are derived from human cells, they may elicit immune responses which may contribute to toxicities or enhanced EV clearance. Furthermore, EVs from different cell sources or EVs comprising various cargo may differ with respect to immunogenicity or toxicity. To assess EV-induced immune response and toxicity, we dosed C57BL/6 mice with EVs intravenously and intraperitoneally for 3 weeks. EVs were harvested from wild type or engineered HEK293T cells which were modified to produce EVs loaded with miR-199a-3p and chimeric proteins. Blood was collected to assess hematology, blood chemistry, and immune markers. Spleen cells were immunophenotyped, and tissues were harvested for gross necropsy and histopathological examination. No signs of toxicity were observed, and minimal evidence of changes in immune markers were noted in mice dosed with engineered, but not with wild type EVs. This study provides a framework for assessment of immunogenicity and toxicity that will be required as EVs from varying cell sources are tested within numerous animal models and eventually in humans.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje