Short-range cytokine gradients to mimic paracrine cell interactions in vitro

Journal of Controlled Release : Official Journal of the Controlled Release Society
Michael AnsorgeTilo Pompe

Abstract

Cell fate decisions in many physiological processes, including embryogenesis, stem cell niche homeostasis and wound healing, are regulated by secretion of small signaling proteins, called cytokines, from source cells to their neighbors or into the environment. Concentration level and steepness of the resulting paracrine gradients elicit different cell responses, including proliferation, differentiation or chemotaxis. For an in-depth analysis of underlying mechanisms, in vitro models are required to mimic in vivo cytokine gradients. We set up a microparticle-based system to establish short-range cytokine gradients in a three-dimensional extracellular matrix context. To provide native binding sites for cytokines, agarose microparticles were functionalized with different glycosaminoglycans (GAG). After protein was loaded onto microparticles, its slow release was quantified by confocal microscopy and fluorescence correlation spectroscopy. Besides the model protein lysozyme, SDF-1 was used as a relevant chemokine for hematopoietic stem and progenitor cell (HSPC) chemotaxis. For both proteins we found gradients ranging up to 50μm from the microparticle surface and concentrations in the order of nM to pM in dependence on loading conce...Continue Reading

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Citations

Jul 13, 2018·Biomaterials Science·Jiranuwat Sapudom, Tilo Pompe
Dec 6, 2018·Advanced Healthcare Materials·Ini-Isabée WitzelJeremy C M Teo
Oct 28, 2017·Scientific Reports·Jiranuwat SapudomTilo Pompe
Jul 24, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Mohsen Khodadadi YazdiMasoud Mozafari

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