Inhibition of complement activation by CD55 overexpression in human induced pluripotent stem cell derived kidney organoids.

Autor:	Gaykema LH; Department of Internal Medicine-Nephrology, Leiden University Medical Center, Leiden, Netherlands.; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands., van Nieuwland RY; Department of Internal Medicine-Nephrology, Leiden University Medical Center, Leiden, Netherlands., Dekkers MC; Department of Internal Medicine-Nephrology, Leiden University Medical Center, Leiden, Netherlands., van Essen MF; Department of Internal Medicine-Nephrology, Leiden University Medical Center, Leiden, Netherlands., Heidt S; Department of Immunology, Leiden University Medical Center, Leiden, Netherlands.; Eurotransplant Reference Laboratory, Leiden University Medical Center, Leiden, Netherlands., Zaldumbide A; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands., van den Berg CW; Department of Internal Medicine-Nephrology, Leiden University Medical Center, Leiden, Netherlands.; The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, Netherlands., Rabelink TJ; Department of Internal Medicine-Nephrology, Leiden University Medical Center, Leiden, Netherlands.; The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, Netherlands., van Kooten C; Department of Internal Medicine-Nephrology, Leiden University Medical Center, Leiden, Netherlands.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Jan 12; Vol. 13, pp. 1058763. Date of Electronic Publication: 2023 Jan 12 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.1058763
Abstrakt:	End stage renal disease is an increasing problem worldwide driven by aging of the population and increased prevalence of metabolic disorders and cardiovascular disease. Currently, kidney transplantation is the only curative option, but donor organ shortages greatly limit its application. Regenerative medicine has the potential to solve the shortage by using stem cells to grow the desired tissues, like kidney tissue. Immune rejection poses a great threat towards the implementation of stem cell derived tissues and various strategies have been explored to limit the immune response towards these tissues. However, these studies are limited by targeting mainly T cell mediated immune rejection while the rejection process also involves innate and humoral immunity. In this study we investigate whether inhibition of the complement system in human induced pluripotent stem cells (iPSC) could provide protection from such immune injury. To this end we created knock-in iPSC lines of the membrane bound complement inhibitor CD55 to create a transplant-specific protection towards complement activation. CD55 inhibits the central driver of the complement cascade, C3 convertase, and we show that overexpression is able to decrease complement activation on both iPSCs as well as differentiated kidney organoids upon stimulation with anti-HLA antibodies to mimic the mechanism of humoral rejection. Competing Interests: 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 Gaykema, van Nieuwland, Dekkers, van Essen, Heidt, Zaldumbide, van den Berg, Rabelink and van Kooten.)
Databáze:	MEDLINE
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