Scientists make progress with growing organs for transplants

Scientists make progress with growing organs for transplants

Researchers from the University of Cambridge have laid the foundations for growing synthetic embryos that could develop a beating heart, gut and brain.

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For over a century, scientists have dreamed of growing human organs sans humans. This technology could put an end to the scarcity of organs for transplants. But that’s just the tip of the iceberg. The capability to grow fully functional organs would revolutionize research. For example, scientists could observe mysterious biological processes, such as how human cells and organs develop a disease and respond (or fail to respond) to medication without involving human subjects.

Recently, a team of researchers from the University of Cambridge has laid the foundations not just for growing functional organs but functional synthetic embryos capable of developing a beating heart, gut, and brain. Their report was published in Nature.


The organoid revolution

In 1981, scientists discovered how to keep stem cells alive. This was a significant breakthrough, as stem cells have notoriously rigorous demands. Nevertheless, stem cells remained a relatively niche research area, mainly because scientists didn’t know how to convince the cells to turn into other cells.

Then, in 1987, scientists embedded isolated stem cells in a gelatinous protein mixture called Matrigel, which simulated the three-dimensional environment of animal tissue. The cells thrived, but they also did something remarkable: they created breast tissue capable of producing milk proteins. This was the first organoid — a clump of cells that behave and function like a real organ. The organoid revolution had begun, and it all started with a boob in Jello.

For the next 20 years, it was rare to find a scientist who identified as an “organoid researcher,” but there were many “stem cell researchers” who wanted to figure out how to turn stem cells into other cells. Eventually, they discovered the signals (called growth factors) that stem cells require to differentiate into other types of cells.

For a human embryo (and its organs) to develop successfully, there needs to be a “dialogue” between these three types of stem cells.

By the end of the 2000s, researchers began combining stem cells, Matrigel, and the newly characterized growth factors to create dozens of organoids, from liver organoids capable of producing the bile salts necessary for digesting fat to brain organoids with components that resemble eyes, the spinal cord, and arguably, the beginnings of sentience.

Synthetic embryos

Organoids possess an intrinsic flaw: they are organ-like. They share some characteristics with real organs, making them powerful tools for research. However, no one has found a way to create an organoid with all the characteristics and functions of a real organ. But Magdalena Żernicka-Goetz, a developmental biologist, might have set the foundation for that discovery.

Żernicka-Goetz hypothesized that organoids fail to develop into fully functional organs because organs develop as a collective. Organoid research often uses embryonic stem cells, which are the cells from which the developing organism is created. However, there are two other types of stem cells in an early embryo: stem cells that become the placenta and those that become the yolk sac (where the embryo grows and gets its nutrients in early development). For a human embryo (and its organs) to develop successfully, there needs to be a “dialogue” between these three types of stem cells. In other words, Żernicka-Goetz suspected the best way to grow a functional organoid was to produce a synthetic embryoid.

As described in the aforementioned Nature paper, Żernicka-Goetz and her team mimicked the embryonic environment by mixing these three types of stem cells from mice. Amazingly, the stem cells self-organized into structures and progressed through the successive developmental stages until they had beating hearts and the foundations of the brain.

“Our mouse embryo model not only develops a brain, but also a beating heart [and] all the components that go on to make up the body,” said Żernicka-Goetz. “It’s just unbelievable that we’ve got this far. This has been the dream of our community for years and major focus of our work for a decade and finally we’ve done it.”

If the methods developed by Żernicka-Goetz’s team are successful with human stem cells, scientists someday could use them to guide the development of synthetic organs for patients awaiting transplants. It also opens the door to studying how embryos develop during pregnancy.

This article originally appeared on Big Think, home of the brightest minds and biggest ideas of all time.

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Peter Rogers
Dr. Peter Rogers grew up milking cows and building barns. This provided him the transferable skills necessary for a smooth transition into academic research. Three years of genetics research led to six years of immunology research, which led to a Ph.D. from Auburn University. That led to three and half years of instructional design research at Tufts University School of Medicine. His expertise includes biomedical sciences & technology, social determinants of health, bovine birthing, training & development, and cognitive psychology. He’s taught dozens of university courses, ranging from Principles of Biology to Advanced Medical Immunology. He is currently co-writing a book with his father, George Rogers, called "How to Correctly Hold a Flashlight: A Disagreement in Academic and Agricultural Perspectives."
Why you should (virtually) care

Virtual-first care, or V1C, could increase the quality of healthcare and make it more patient-centric by letting patients combine in-person visits with virtual options such as video for seeing their care providers.

(© Elnur/Fotolia)

As the pandemic turns endemic, healthcare providers have been eagerly urging patients to return to their offices to enjoy the benefits of in-person care.

But wait.

The last two years have forced all sorts of organizations to be nimble, adaptable and creative in how they work, and this includes healthcare providers’ efforts to maintain continuity of care under the most challenging of conditions. So before we go back to “business as usual,” don’t we owe it to those providers and ourselves to admit that business as usual did not work for most of the people the industry exists to help? If we’re going to embrace yet another period of change – periods that don’t happen often in our complex industry – shouldn’t we first stop and ask ourselves what we’re trying to achieve?

Certainly, COVID has shown that telehealth can be an invaluable tool, particularly for patients in rural and underserved communities that lack access to specialty care. It’s also become clear that many – though not all – healthcare encounters can be effectively conducted from afar. That said, the telehealth tactics that filled the gap during the pandemic were largely stitched together substitutes for existing visit-based workflows: with offices closed, patients scheduled video visits for help managing the side effects of their blood pressure medications or to see their endocrinologist for a quarterly check-in. Anyone whose children slogged through the last year or two of remote learning can tell you that simply virtualizing existing processes doesn’t necessarily improve the experience or the outcomes!

But what if our approach to post-pandemic healthcare came from a patient-driven perspective? We have a fleeting opportunity to advance a care model centered on convenient and equitable access that first prioritizes good outcomes, then selects approaches to care – and locations – tailored to each patient. Using the example of education, imagine how effective it would be if each student, regardless of their school district and aptitude, received such individualized attention.

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Jennifer C. Goldsack & Linette Demers
Jennifer C. Goldsack co-founded and serves as the CEO of the Digital Medicine Society (DiMe), a 501(c)(3) non-profit organization dedicated to advancing digital medicine to optimize human health. Jennifer’s research focuses on applied approaches to the safe, effective, and equitable use of digital technologies to improve health, healthcare, and health research. She is a member of the Roundtable on Genomics and Precision Health at the National Academies of Science, Engineering and Medicine and serves on the World Economic Forum Global Leadership Council on mental health. Previously, Jennifer spent several years at the Clinical Trials Transformation Initiative (CTTI), a public-private partnership co-founded by Duke University and the FDA. There, she led development and implementation of several projects within CTTI’s Digital Program and was the operational co-lead on the first randomized clinical trial using FDA’s Sentinel System. Jennifer spent five years working in research at the Hospital of the University of Pennsylvania, first in Outcomes Research in the Department of Surgery and later in the Department of Medicine. More recently, she helped launch the Value Institute, a pragmatic research and innovation center embedded in a large academic medical center in Delaware. Jennifer earned her master’s degree in chemistry from the University of Oxford, England, her masters in the history and sociology of medicine from the University of Pennsylvania, and her MBA from the George Washington University. Additionally, she is a certified Lean Six Sigma Green Belt and a Certified Professional in Healthcare Quality. Jennifer is a retired athlete, formerly a Pan American Games Champion, Olympian, and World Championship silver medalist. ___________________________________________________________________________ Linette Demers leads IMPACT, a DiMe initiative dedicated to advancing high value, evidence-based virtual first care for patients, healthcare providers, and payers. Previously, Linette was responsible for commercialization, entrepreneurship and capital formation programs at Life Science Washington and WINGS Angels. Her 20 year career in healthcare spans strategy, business development, and population health management in oncology care at Fred Hutch, and management consulting at Sg2. Linette holds a PhD in Chemistry and a BS in Health Economics and Outcomes Research.
Podcast: The future of brain health with Percy Griffin

Percy Griffin, director of scientific engagement for the Alzheimer’s Association, joins Leaps.org to discuss the present and future of the fight against dementia.

The Alzheimer's Association

Today's guest is Percy Griffin, director of scientific engagement for the Alzheimer’s Association, a nonprofit that’s focused on speeding up research, finding better ways to detect Alzheimer’s earlier and other approaches for reducing risk. Percy has a doctorate in molecular cell biology from Washington University, he’s led important research on Alzheimer’s, and you can find the link to his full bio in the show notes, below.

Our topic for this conversation is the present and future of the fight against dementia. Billions of dollars have been spent by the National Institutes of Health and biotechs to research new treatments for Alzheimer's and other forms of dementia, but so far there's been little to show for it. Last year, Aduhelm became the first drug to be approved by the FDA for Alzheimer’s in 20 years, but it's received a raft of bad publicity, with red flags about its effectiveness, side effects and cost.

Meanwhile, 6.5 million Americans have Alzheimer's, and this number could increase to 13 million in 2050. Listen to this conversation if you’re concerned about your own brain health, that of family members getting older, or if you’re just concerned about the future of this country with experts predicting the number people over 65 will increase dramatically in the very near future.

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Matt Fuchs
Matt Fuchs is the host of the Making Sense of Science podcast and served previously as the editor-in-chief of Leaps.org. He writes as a contributor to the Washington Post, and his articles have also appeared in the New York Times, WIRED, Nautilus Magazine, Fortune Magazine and TIME Magazine. Follow him @fuchswriter.