Multiscale microenvironmental perturbation of pluripotent stem cell fate and self-organization
Open accessAbstract
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.
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Manipulating synthetic hydrogels using methods such as electrospinning, photopatterning, spraying of microspheres, inkjet and 3D printing, or microfluidic channels enables control over the shape and size of the organoids.
“Manipulating synthetic hydrogels using methods such as electrospinning125, photopatterning126,127, spraying of microspheres128, inkjet and 3D printing129, or microfluidic channels130 further enables control over the shape and size of the organoids.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [130]
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- Authors
- Tabata, Y., & Lutolf, M. P.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- ORCID
- Tabata, Yoji
- Venue
- Scientific Reports
- Published
- 2017-03-17
- Volume
- 7
- Issue
- 1
- Pages
- 44711-44711
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5356187
- OpenAlex
- W2595041682
- Cited by
- 37
- References
- 40
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 5 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 6 · 2018: 5 · 2017: 2
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- organoids, microfluidics, hydrogel encapsulation, mouse embryonic stem cells, neuronal differentiation, leukemia inhibitory factor, apical-basal polarity, epithelial cysts, intercellular communication, self-patterning
- MeSH terms
- Mouse Embryonic Stem Cells, Animals, Cells, Cultured, Diffusion, Extracellular Matrix, Solubility, Cell Lineage, Pluripotent Stem Cells, Microfluidics, Mice, Leukemia Inhibitory Factor, Microtechnology, Cellular Microenvironment
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