In vitro evaluation of immune responses to bacterial hydrogels for the development of living therapeutic materials.

Autor: Yanamandra AK; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany; INM - Leibniz Institute for New Materials, Saarbrücken, Germany., Bhusari S; INM - Leibniz Institute for New Materials, Saarbrücken, Germany; Chemistry Department, Saarland University, 66123 Saarbrücken, Germany., Del Campo A; INM - Leibniz Institute for New Materials, Saarbrücken, Germany; Chemistry Department, Saarland University, 66123 Saarbrücken, Germany., Sankaran S; INM - Leibniz Institute for New Materials, Saarbrücken, Germany. Electronic address: shrikrishnan.sankaran@leibniz-inm.de., Qu B; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany; INM - Leibniz Institute for New Materials, Saarbrücken, Germany. Electronic address: bin.qu@uks.eu.
Jazyk: angličtina
Zdroj: Biomaterials advances [Biomater Adv] 2023 Oct; Vol. 153, pp. 213554. Date of Electronic Publication: 2023 Jul 13.
DOI: 10.1016/j.bioadv.2023.213554
Abstrakt: In living therapeutic materials (LTMs), organisms genetically programmed to produce and deliver drugs are encapsulated in porous matrices acting as physical barriers between the therapeutic organisms and the host cells. LTMs consisting of engineered E. coli encapsulated in Pluronic F127-based hydrogels have been frequently used in LTM designs but their immunogenicity has not been tested. In this study, we investigate the response of human peripheral blood mononuclear cells (PBMCs) exposed to this bacteria/hydrogel combination. The release of inflammation-related cytokines and cytotoxic proteins and the subsets of natural killer cells and T cells were examined. Encapsulation of the bacteria in hydrogels considerably lowers their immunogenicity. ClearColi, an endotoxin-free variant of E. coli, did not polarize NK cells into the more cytolytic CD16 dim subset as E. coli. Our results demonstrate that ClearColi-encapsulated hydrogels generate low immunogenic response and are suitable candidates for the development of LTMs for in vivo testing to assess a potential clinical use. Nevertheless, we observed a stronger immune response (elevated levels of IFNγ, IL-6 and cytotoxic proteins) in pro-inflammatory PBMCs characterized by a high spontaneous release of IL-2. This highlights the need to identify recipients who have a higher likelihood of experiencing undesired immune responses to LTMs with IL-2 serving as a potential predictive marker. Additionally, including anti-inflammatory measures in living therapeutic material designs could be beneficial for such recipients.
Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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