Multiscale microenvironmental perturbation of pluripotent stem cell fate and self-organization
| Autor: | Yoji Tabata, Matthias P. Lutolf |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Pluripotent Stem Cells
0301 basic medicine Microfluidics Biology Leukemia Inhibitory Factor Article Diffusion Mice 03 medical and health sciences Organoid Animals Cell Lineage Induced pluripotent stem cell Cells Cultured Multidisciplinary Mouse Embryonic Stem Cells Embryonic stem cell In vitro Extracellular Matrix Cell biology Multicellular organism 030104 developmental biology Cellular Microenvironment Solubility Microtechnology Neural differentiation Stem cell Leukemia inhibitory factor |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | The combination of microfluidics with engineered three-dimensional (3D) matrices can bring new insights into the fate regulation of stem cells and their self-organization into organoids. Although there has been progress in 3D stem cell culturing, most existing in vitro methodologies do not allow for mimicking of the spatiotemporal heterogeneity of stimuli that drive morphogenetic processes in vivo. To address this, we present a perfusion-free microchip concept for the in vitro 3D perturbation of stem cell fate. Stem cells are encapsulated in a hydrogel compartment that is flanked by open reservoirs for the diffusion-driven generation of biomolecule gradients. Juxtaposing additional compartments bearing supportive cells enables investigating the influence of long range cell-cell communication. We explore the utility of the microchips in manipulating early fate choices and self-organizing characteristics of 3D-cultured mouse embryonic stem cells (mESCs) under neural differentiation conditions and exposure to gradients of leukemia inhibitory factor (LIF). mESCs respond to LIF gradients in a spatially dependent manner. At higher LIF concentrations, multicellular colonies maintain pluripotency in contrast, at lower concentrations, mESCs develop into apicobasally polarized epithelial cysts. This versatile system can help to systematically explore the role of multifactorial microenvironments in promoting self-patterning of various stem cell types. |
| Databáze: | OpenAIRE |
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