Human whole-blood culture system for ex vivo characterization of designer-cell function.

Biotechnology and Bioengineering
Lina SchukurMartin Fussenegger

Abstract

Encapsulated designer cells implanted into mice are currently used to validate the efficacy of therapeutic gene networks for the diagnosis and treatment of various human diseases in preclinical research. Because many human conditions cannot be adequately replicated by animal models, complementary and alternative procedures to test future treatment strategies are required. Here we describe a novel approach utilizing an ex vivo human whole-blood culture system to validate synthetic biology-inspired designer cell-based treatment strategies. The viability and functionality of transgenic mammalian designer cells co-cultured with primary human immune cells were characterized. We demonstrated that transgenic mammalian designer cells required adequate insulation from the human blood microenvironment to maintain viability and functionality. The biomaterial alginate-(poly-l-lysine)-alginate used to encapsulate the transgenic designer cells did neither affect the viability of primary granulocytes and lymphocytes nor the functionality of lymphocytes. Additionally, alginate-encapsulated transgenic designer cells remained responsive to the release of the pro-inflammatory cytokine tumor necrosis factor (TNF) from the whole-blood culture upon ...Continue Reading

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Citations

Dec 26, 2015·Integrative Biology : Quantitative Biosciences From Nano to Macro·Anton DobrinMartin Fussenegger
May 3, 2016·Current Opinion in Biotechnology·Mingqi XieMartin Fussenegger
Jun 25, 2016·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Lina Schukur, Martin Fussenegger
Jun 3, 2018·Nature Reviews. Molecular Cell Biology·Mingqi Xie, Martin Fussenegger

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