Next-gen organoids grow and function like real tissues

Date:
September 16, 2020
Source:
Ecole Polytechnique Fe'de'rale de Lausanne
Summary:
Bioengineers have created miniature intestines in a dish that
match up anatomically and functionally to the real thing better
than any other lab-grown tissue models. The biological complexity
and longevity of the new organoid technology is an important step
towards enabling drug testing, personalized medicine, and perhaps,
one day, transplantations.



FULL STORY ========================================================================== Organoids are fast-becoming one of the most cutting-edge tools of
modern life sciences. The idea is to use stem cells to build miniature
tissues and organs that accurately resemble and behave like their real counterparts.


==========================================================================
One can immediately appreciate the value of organoids for both research
and medicine: from basic biological research to drug development and
testing, organoids could complement animal testing by providing healthy
or diseased human tissues, expediting the lengthy journey from lab to
clinical trial.

Beyond that, there is already the whisper of organoid technology perhaps
being used for replacing damaged tissues or even organs in the future:
take stems cells from the patient and grow them into a new liver, heart, kidney, or lung.

So far, established methods of making organoids come with considerable drawbacks: stem cells develop uncontrollably into circular and closed
tissues that have a short lifespan, as well as non-physiological size
and shape, all of which result in overall anatomical and/or physiological inconsistency with real-life organs.

Now, scientists from the group led by Matthias Lu"tolf at EPFL's
Institute of Bioengineering have found a way to "guide" stem cells to
form an intestinal organoid that looks and functions just like a real
tissue. Published in Nature, the method exploits the ability of stem
cells to grow and organize themselves along a tube-shaped scaffold that
mimics the surface of the native tissue, placed inside a microfluidic
chip (a chip with little channels in which small amounts of fluids can
be precisely manipulated).

The EPFL researchers used a laser to sculpt this gut-shaped scaffold
within a hydrogel, a soft mix of crosslinked proteins found in the gut's extracellular matrix supporting the cells in the native tissue. Aside
from being the substrate on which the stem cells could grow, the hydrogel
thus also provides the form or "geometry" that would build the final
intestinal tissue.

Once seeded in the gut-like scaffold, within hours, the stem cells
spread across the scaffold, forming a continuous layer of cells with
its characteristic crypt structures and villus-like domains. Then came
the surprise: the scientists found that, the stem cells just "knew"
how to arrange themselves in order to form a functional tiny gut.

"It looks like the geometry of the hydrogel scaffold, with its
crypt-shaped cavities, directly influences the behavior of the stem
cells so that they are maintained in the cavities and differentiate in
the areas outside, just like in the native tissue," says Lu"tolf. The
stem cells didn't just adopt to the shape of the scaffold, they produced
all the key differentiated cell types found in the real gut, with some
rare and specialized cell types normally not found in organoids.

Intestinal tissues are known for the highest cell turnover rates in the
body, resulting in a massive amount of shed dead cells accumulating
in the lumen of the classical organoids that grow as closed spheres
and require weekly breaking down into small fragments to maintain
them in culture. "The introduction of a microfluidic system allowed
us to efficiently perfuse these mini-guts and establish a long-lived homeostatic organoid system in which cell birth and death are balanced,"
says Mike Nikolaev, the first author of the paper.

The researchers demonstrate that these miniature intestines share
many functional features with their in vivo counterparts. For example,
they can regenerate after massive tissue damage and they can be used to
model inflammatory processes or host-microbe interactions in a way not previously possible with any other tissue model grown in the laboratory.

In addition, this approach is broadly applicable for the growth of
miniature tissues from stem cells derived from other organs such as the
lung, liver or pancreas, and from biopsies of human patients. "Our work
shows that tissue engineering can be used to control organoid development
and build next-gen organoids with high physiological relevance, opening up exciting perspectives for disease modelling, drug discovery, diagnostics
and regenerative medicine," says Lu"tolf.


========================================================================== Story Source: Materials provided by
Ecole_Polytechnique_Fe'de'rale_de_Lausanne. Original written by Nik Papageorgiou. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Mikhail Nikolaev, Olga Mitrofanova, Nicolas Broguiere, Sara Geraldo,
Devanjali Dutta, Yoji Tabata, Nathalie Brandenberg,
Irina Kolotuev, Nikolche Gjorevski, Hans Clevers, Matthias
P. Lutolf. Homeostatic mini- intestines through scaffold-guided
organoid morphogenesis. Nature, 2020 DOI: 10.1038/s41586-020-2724-8 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200916113529.htm

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