«The use of a mouse tumor - derived matrix would limit any future
applications of these organoid technologies in humans, and this work opens the door to research directed specifically for clinical applications,» noted Asma Nusrat, study co-author and the Aldred Scott Warthin Professor and Director of Experimental Pathology in the University of Michigan's School of Medicine.
BAR HARBOR, MAINE — The MDI Biological Laboratory in Bar Harbor, Maine, has announced that it will offer a one - week intensive course May 27 through June 2, 2018 entitled «Applications
of Organoid Technology» in partnership with Hubrecht Organoid Technology (The HUB), a non-profit organization based in Utrecht, Netherlands.
Perhaps one approach to reach this goal is the combined
use of organoid engraftment techniques and pharmacotherapy with small molecules that are capable of stimulating tissue regeneration, such as the ones recently discovered at the MDI Biological Laboratory (22).
In addition to allowing
growth of organoids within the engineered hydrogel in a tissue culture incubator, the research team demonstrated that the hydrogel could act like glue, allowing organoids to stick in place and contribute to wound healing when transplanted into an injured mouse intestine.
Meanwhile, biologists elsewhere were whipping up other
types of organoids, starting instead with adult stem cells.
«The great
advantage of organoids is that they are essentially avatars of a patient's tumor,» said study leader Michael M. Shen, PhD, professor of medicine, genetics & development, urology, and systems biology at Columbia University Vagelos College of Physicians and Surgeons.
Thirdly, the current, almost universal dependency
of organoid culture on the use of Matrigel as a replacement for the function of the extracellular basement matrix in providing structural support and survival signals to the epithelial cells hampers clinical application, considering its origin from a mouse sarcoma cell line, its poorly defined composition and its mechanical rigidity after plating.
Stem cell - derived organoids cultured two - dimensionally: The
benefits of organoids with the dosing convenience of epithelial cell lines
The directors
of the organoid course are Hugo de Jonge, Ph.D, professor at Erasmus University Medical Center (Erasmus MC) in Rotterdam, Netherlands, and a visiting professor at the MDI Biological Laboratory, and Robert Vries, Ph.D., managing director at Foundation Hubrecht Organoid Technology.
We see some cell death even in the
edge of the organoids starting at 10 weeks, which becomes really dramatic over time.
The only way the team can be sure they have grown the equivalent of a fetal brain would be to genetically test individual cells from different
regions of the organoid, and compare them to those of human fetus, says Christof Koch at the Allen Institute for Brain Science in Seattle.
One concern raised by the human brain organoid implants «is that functional integration
[of the organoids] into the central nervous system of animals can in principle alter an animal's behavior or needs,» said bioethicist Jonathan Kimmelman of McGill University in Montreal.
In the organoids, the scientists found such mechanical instability in two places: the cytoskeleton — the internal skeleton — of the cells in the
center of the organoid contracted, and the nuclei of the cells near the surface expanded.
But Dr. Eyal Karzbrun, a member of the Reiner Lab, had to put a bit of a damper on their enthusiasm: the
sizes of the organoids they obtained were far from uniform; with no blood vessels, the insides did not have a steady supply of nutrients and started to die; and the thickness of the tissue got in the way of the optical imaging and microscope tracking.
The researchers use a technique called «optical metabolic imaging» to measure the activity
level of the organoids.
According to his unpublished findings, when he puts glioblastoma cells from patients into lab dishes with brain organoids, the cells attach to the
surface of the organoids, burrow into them, and within 24 to 48 hours grow into a mass that eventually «looks exactly like what happened in the patient's own brain,» Fine said.
By carefully tweaking the hydrogel's properties, they discovered that separate
stages of the organoid formation process require different mechanical environments and biological components.
The various methods create different
kinds of organoids, each with advantages and drawbacks.
To turn these cellular LEGOs into
arrays of organoids that can be used for research, Gartner's team lays down the cells in layers, with multiple sets of cells designed to stick to particular partners.
Not only does this let them build up complex tissue components like the mammary gland, but also to experiment with specifically adding in a single cell with a known cancer mutation to different
parts of the organoid to observe its effects.
High - resolution
imaging of the organoid identifies functioning neurons and their signal - carrying extensions — axons and dendrites — as well as astrocytes, oligodendrocytes and microglia.
«The ultimate test of
functionality of an organoid is to show that it can integrate into a host,» molecular geneticist Hans Clevers of the Hubrecht Institute in Utrecht, the Netherlands writes in an email to The Scientist.
An in vivo maturation step mediates the
generation of organoids resembling mature intestinal tissue from human pluripotent stem cells
Next - generation «designer matrices» such as hybrid polyethylene glycol hydrogels or microengineered collagen scaffolds, combined with a well - defined set of laminins, may better fulfill the niche
requirements of organoids and may be customized for a specific type of tissue / organoid (2,6).
The result, he notes, confirms what he finds «the most amazing
phenomenon of organoids — their almost unstoppable drive to reach ever increasing levels of self - organization.»
The new biomedical innovation course, which will take place at the laboratory's Maine campus, is geared to advanced graduate students, post-doctoral trainees and researchers at all levels who want to learn the
basics of organoid culture and the most recent developments in the organoid field.
That ability may come in the next
frontier of organoid development, as researchers look to culture various types of stem cells together to create organoids that incorporate additional features.
Many scientists, concerned about the finite
lifespan of organoids, questioned whether they would be useful for research on conditions of aging.
Researchers exposed another
set of organoids derived from the same Alzheimer's patients to experimental compounds known to prevent the secretion or accumulation of amyloid, and they discovered that the plaques didn't form.
One study showed that the
implementation of these organoids in mice with diseased colons can repair injury, suggesting the therapeutic potential of this research for Crohn's disease.
«There is another concern about «embryoids,» which are a special
class of organoid containing all three layers of embryonic tissue: the ectoderm, mesoderm, and endoderm,» says Koehler.
Second, their biochemical complexity makes them very difficult to fine - tune for studying the effect of different parameters (e.g. biological molecules, mechanical properties, etc.) on the
growth of organoids.
The MDI Biological Laboratory in Bar Harbor, Maine, has announced that it will offer a one - week intensive course May 28 through June 3 entitled «
Applications of Organoid Technology» in partnership with Hubrecht Organoid Technology (The HUB), a non-profit organization based in Utrecht, Netherlands.
Within a specialized growth environment, the stem cells, either adult or embryonic, depending on the tissue needed, are stimulated to grow and specialize into specific
types of organoids.
The MDI Biological Laboratory has announced that it will offer a one - week intensive course May 27 through June 2, 2018, entitled «Applications
of Organoid Technology» in partnership with Hubrecht Organoid Technology (The HUB), a non-profit organization based in Utrecht, Netherlands.
This poster describes the isolation and maintenance in culture of pluripotent stem cells, their differentiation, and the generation and potential
uses of organoids.
«The great
advantage of organoids is that they are essentially avatars of a patient's tumor,» study coauthor Michael Shen, a geneticist at Columbia University, says in a press release.
That work underscores a chief
benefit of all organoids — that they can be used to try out potential therapies, with results that are likely to be similar to what would happen in people when a treatment advances to human clinical trials.
Hans Clevers, the head of the Hubrecht Laboratory in Utrecht, the Netherlands, has pioneered the
development of organoids, miniature versions of human organs that are transforming science and medicine.
By combining engineered polymeric materials known as hydrogels with complex intestinal tissue known as organoids — made from human pluripotent stem cells — researchers have taken an important step toward creating a new technology for controlling the growth
of these organoids and using them for treating wounds in the gut that can be caused by disorders such as inflammatory bowel disease (IBD).