Bioengineering approaches to guide stem cell-based organogenesis

Abstract

During organogenesis, various molecular and physical signals are orchestrated in space and time to sculpt multiple cell types into functional tissues and organs. The complex and dynamic nature of the process has hindered studies aimed at delineating morphogenetic mechanisms in vivo, particularly in mammals. Recent demonstrations of stem cell-driven tissue assembly in culture offer a powerful new tool for modeling and dissecting organogenesis. However, despite the highly organotypic nature of stem cell-derived tissues, substantial differences set them apart from their in vivo counterparts, probably owing to the altered microenvironment in which they reside and the lack of mesenchymal influences. Advances in the biomaterials and microtechnology fields have, for example, afforded a high degree of spatiotemporal control over the cellular microenvironment, making it possible to interrogate the effects of individual microenvironmental components in a modular fashion and rapidly identify organ-specific synthetic culture models. Hence, bioengineering approaches promise to bridge the gap between stem cell-driven tissue formation in culture and morphogenesis in vivo, offering mechanistic insight into organogenesis and unveiling powerful new models for drug discovery, as well as strategies for tissue regeneration in the clinic. We draw on several examples of stem cellderived organoids to illustrate how bioengineering can contribute to tissue formation ex vivo. We also discuss the challenges that lie ahead and potential ways to overcome them.

Creating to understand – developmental biology meets engineering in Paris

“…The field has developed numerous approaches to combine stem cells with biomaterials (e.g. functionalized hydrogels; Gjorevski et al, 2014) and biomimetic environments (e.g. microfluidic-based bioreactors; Andersson and van den Berg, 2004), and thus has a lot to offer.…”

Light‐Patterned RNA Interference of 3D‐Cultured Human Embryonic Stem Cells

“…NIR laser irradiation was performed through z-stacks of the cell mass with 1.4 µm intervals, and each z-stack (512 × 512 pixels) was scanned line-by-line Biological processes are stimulated by various molecular and physical signals orchestrated in space and time. [1][2][3][4] Tissue and organ generation in vitro for transplant therapy and disease modeling for drug screening [5] are especially demanding for precise control over 3D patterning of different cell types. [2,4,6,7] Advances in this area include the controlled differentiation of pluripotent or multipotent stem cells cultured in 3D matrices followed by self-organization into tissues in vitro.…”

“…[1][2][3][4] Tissue and organ generation in vitro for transplant therapy and disease modeling for drug screening [5] are especially demanding for precise control over 3D patterning of different cell types. [2,4,6,7] Advances in this area include the controlled differentiation of pluripotent or multipotent stem cells cultured in 3D matrices followed by self-organization into tissues in vitro. [1,[8][9][10][11] However, current methods for organoid formation have insufficient control over the course of the morphogenetic processes and the resulting structures inadequately replicate native tissues.…”

“…[1,[8][9][10][11] However, current methods for organoid formation have insufficient control over the course of the morphogenetic processes and the resulting structures inadequately replicate native tissues. [2,4] Microfluidic and nanotopographic patterning approaches establish some organ-level functions ex vivo, but lack the dimensionality to approximate developing tissues. [2,[12][13][14] Light is an ideal stimulus for perturbing the spatiotemporal dynamics of signals in living cells and organisms with high resolution.…”

“…[2,4] Microfluidic and nanotopographic patterning approaches establish some organ-level functions ex vivo, but lack the dimensionality to approximate developing tissues. [2,[12][13][14] Light is an ideal stimulus for perturbing the spatiotemporal dynamics of signals in living cells and organisms with high resolution. [15][16][17] The light-based optogenetic field has answered real biological questions [16] and developed tools for light-controlled genome editing and gene transfection.…”