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Homeostatic mini-intestines through scaffold-guided organoid morphogenesis.
Journal article

Homeostatic mini-intestines through scaffold-guided organoid morphogenesis.

  • Nikolaev M Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Mitrofanova O Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Broguiere N Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Geraldo S Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Dutta D Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Tabata Y Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Elci B Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Brandenberg N Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Kolotuev I Electron Microscopy Facility, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
  • Gjorevski N Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Clevers H Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Utrecht, The Netherlands.
  • Lutolf MP Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. matthias.lutolf@epfl.ch.
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  • 2020-09-17
Published in:
  • Nature. - 2020
Animals
Body Patterning
Cell Differentiation
Cell Lineage
Cryptosporidium parvum
Homeostasis
Human Embryonic Stem Cells
Human Umbilical Vein Endothelial Cells
Humans
Intestines
Mice
Models, Biological
Morphogenesis
Organoids
Regeneration
Regenerative Medicine
Stem Cells
Tissue Culture Techniques
Tissue Engineering
Tissue Scaffolds
English Epithelial organoids, such as those derived from stem cells of the intestine, have great potential for modelling tissue and disease biology1-4. However, the approaches that are used at present to derive these organoids in three-dimensional matrices5,6 result in stochastically developing tissues with a closed, cystic architecture that restricts lifespan and size, limits experimental manipulation and prohibits homeostasis. Here, by using tissue engineering and the intrinsic self-organization properties of cells, we induce intestinal stem cells to form tube-shaped epithelia with an accessible lumen and a similar spatial arrangement of crypt- and villus-like domains to that in vivo. When connected to an external pumping system, the mini-gut tubes are perfusable; this allows the continuous removal of dead cells to prolong tissue lifespan by several weeks, and also enables the tubes to be colonized with microorganisms for modelling host-microorganism interactions. The mini-intestines include rare, specialized cell types that are seldom found in conventional organoids. They retain key physiological hallmarks of the intestine and have a notable capacity to regenerate. Our concept for extrinsically guiding the self-organization of stem cells into functional organoids-on-a-chip is broadly applicable and will enable the attainment of more physiologically relevant organoid shapes, sizes and functions.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/1055
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