Dissecting the stem cell niche with organoid models: an engineering-based approach

Abstract

For many tissues, single resident stem cells grown in vitro under appropriate three-dimensional conditions can produce outgrowths known as organoids. These tissues recapitulate much of the cell composition and architecture of the in vivo organ from which they derive, including the formation of a stem cell niche. This has facilitated the systematic experimental manipulation and single-cell, highthroughput imaging of stem cells within their respective niches. Furthermore, emerging technologies now make it possible to engineer organoids from purified cellular and extracellular components to directly model and test stem cell-niche interactions. In this Review, we discuss how organoids have been used to identify and characterize stem cell-niche interactions and uncover new niche components, focusing on three adult-derived organoid systems. We also describe new approaches to reconstitute organoids from purified cellular components, and discuss how this technology can help to address fundamental questions about the adult stem cell niche.

Organoids – New Models for Host–Helminth Interactions

“…forces, and the cellular niche refers to the resident immune and stromal cells embedded in the ECM that provide signaling clues to maintain stem cell division and differentiation [12,14,15]. Current organoid culture conditions combine an ECM support with exogenous growth factors and morphogens (both promoters and inhibitors) that direct the division and differentiation of daughter cells into the multiple cellular populations present in the targeted organ [1,2,10,11,16].…”

“…New engineering-based approaches for control over organoid composition, size, spatial organization, luminal accessibility, chemical gradients, and biomechanical forces are being developed [1,3,15,53,57,58]. These include 3D-bioprinting, chemically programmed assembly and defined ECM, microwell arrays, droplet-based microfluidics, peristaltic pumps, and bioreactors [3,15,16,58,59]. These approaches offer increasing control over physiological conditions and will enable a better understanding of how tissue architecture influences the cellular responses during helminth infection.…”

Organoids: a Special Issue

“…Indeed, organoids can be used to interrogate the driving principles of morphogenesis, and the opportunity for synergy between organoid biology and materials science is boundless. In their Spotlight article, Dahl-Jensen and Grapin-Botton (2017) discuss how the field of physics can help our understanding of organoid formation, while Gartner and colleagues (Murrow et al, 2017) review engineering-based approaches to dissect stem cell-niche interactions. The organoid field arguably grew out of seminal studies in the 1900s based on the capacity for disassociated cells to reform structure.…”

Human embryo research and the 14-day rule

“…Since then, directed differentiation protocols, which are largely based on embryological principles and emulate normal developmental pathways, have facilitated the large-scale production of a range of cell types for research and therapy, mostly in two-dimensional culture platforms. It is not difficult to envision that this directed differentiation could be implemented in three-dimensional cultures by engineering microwells, microfluidic chambers, and smart surfaces to yield spatially and temporally controlled delivery of growth factors and extracellular matrices, thus reconstructing the embryonic environment to promote key morphogenetic processes (Murrow et al, 2017). Today, single-cell transcriptional profiling enables comparison of stem cell cultures in vitro to the human pre-implantation embryo, non-human primate post-implantation stages, and human embryonic and foetal tissues at later stages of development (4-5 weeks onward), allowing validation of the culture model.…”