Toxicological Profile of Umbilical Cord Blood-Derived Small Extracellular Vesicles
Autor: | Filipe V. Duarte, Silvia C Rodrigues, Claudia F Gomes, Joana Simões-Correia, Ricardo Pires das Neves, Patricia C. Freire, Renato M. S. Cardoso |
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Rok vydání: | 2021 |
Předmět: |
Kidney
business.industry Process Chemistry and Technology Chemical technology Filtration and Separation Spleen TP1-1185 Pharmacology Umbilical cord Peripheral blood mononuclear cell Umbilical vein Article EV toxicity Chemical engineering medicine.anatomical_structure In vivo Cell culture Toxicity EV therapeutics medicine umbilical cord blood Chemical Engineering (miscellaneous) TP155-156 business extracellular vesicles |
Zdroj: | Membranes Membranes, Vol 11, Iss 647, p 647 (2021) Volume 11 Issue 9 |
ISSN: | 2077-0375 |
Popis: | The development and adoption of cell therapies has been largely limited by difficulties associated with their safety, handling and storage. Extracellular vesicles (EV) have recently emerged as a likely mediator for the therapeutic effect of cells, offering several advantages over cell therapies. Due to their small size and inability to expand and metastasize, EV are generally considered safer than cell transplantation. Nevertheless, few studies have scrutinized the toxicity profile of EV, particularly after repeated high dose administration. The present study aimed to evaluate a preparation of small EV obtained from umbilical cord blood mononuclear cells (UCB-MNC-sEV) for its cytotoxicity in different cell lines, as well as its differential accumulation, distribution and toxicity following repeated intravenous (IV) administrations in a rodent model. In vitro, repeated sEV exposure in concentrations up to 1×1011 particles/ml had no deleterious impact on the viability or metabolic activity of peripheral blood mononuclear cells, THP-1 monocytes, THP-1-derived macrophages, normal dermal human fibroblasts or human umbilical vein endothelial cells. DiR-labeled sEV, injected IV for four weeks in healthy rats, were detected in clearance organs, particularly kidneys, spleen and liver, similarly to control dye. Moreover, repeated administrations during six and twelve weeks of up to 1×1010 total particles of sEV-dye were well tolerated, with no changes in general hematological cell counts, or kidney and liver toxicity markers. Importantly, unlabeled sEV likewise did not induce significant alterations in cellular and biochemical blood parameters, nor any morphological changes in heart, kidney, lung, spleen, or liver tissue. In sum, our data shows that UCB-MNC-sEV have no significant toxicity in vitro or in vivo, even when administered repeatedly at high concentrations, therefore confirming their safety profile and potential suitability for future clinical use. |
Databáze: | OpenAIRE |
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