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Growing Spare Parts From Stem Cells

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Organoids Research

Mini-Organs Could Give a Big Boost to Biomedical Research

Why you should care

Because these mini-organs could streamline drug testing and serve as custom-made, lifesaving “spare parts.”

In petri dishes and bioreactors around the world, a tiny revolution is unfolding.

Scientists are growing tiny brains, livers, kidneys and other organs — aka “organoids” — that look and function much like their full-sized counterparts. These fun-sized organs could give a serious boost to biomedical research, helping to unravel diseases in ways that aren’t possible in the animal models or flasks of cells usually used in research and drug testing. Some researchers are even designing “humans on a chip,” mini-versions of every organ system, all on a credit card-sized chip. Eventually, scientists hope to use organoids — custom-made from patients’ own stem cells — to replace diseased organ parts.

Which could be a huge step toward solving the organ shortage problem. An average of 18 people in the U.S. die every day waiting for a “match,” or a donor whose immune system is chemically similar to their own, to ensure their bodies don’t reject the new organ. Since organoids come from patients’ own cells, they shouldn’t trigger tissue rejection, which can be fatal.

Researchers at Vienna’s Institute of Molecular Biotechnology coaxed human iPS cells derived from skin to develop into brain-like organoids.

But it could be years before organoids can solve that big problem. So far, the mini-organs still lack the blood vessels needed to supply their internal cells with food and oxygen, which means they can’t grow very big. Although more complex than a flask of cells, they lack the full diversity of cell types, tissue complexity and developmental level of actual organs.

What could be closer: using organoids to replace parts of organs.

Computer generated image of cell

Source: Madeline A. Lancaster

A cross-section of a brain-like clump of neural cells derived from human stem cells

And testing drugs on the organoids is a near-term possibility — offering a faster, cheaper pathway from lab to patient. “You can test [a drug’s] toxicity and efficacy before you ever get it in a patient,” says James Wells, a developmental biologist at Cincinnati Children’s Hospital Medical Center. A drug takes about 12 years to progress from the lab to the clinic and costs billions of dollars — yet a whopping 95 percent of the drugs tested in humans fail to be both effective and safe.

Wells is working on an initiative led by the NIH, FDA and Defense Advanced Research Projects Agency to integrate different organoid systems — connected via channels — onto a 3-D chip. Several chips could be engineered from a variety of people to represent a wide swath of the population. Or scientists could tailor drugs to individual patients, generating organoids from their own cells.

Organoids are made from stem cells bathed in nutrients and spun in a bioreactor. Researchers often use rodent embryonic stem cells, which can mature into any cell type. Those working with human cells often reprogram mature cells to behave like embryonic stem cells, forming induced pluripotent stem cells (iPS cells).

“Then they self-organize,” says Anne Grapin-Botton, a developmental biologist at the University of Copenhagen. Given the right nutrient mix, the stem cells mature into different cell types and arrange themselves into a 3-D organoid structure.

Grapin-Botton hopes her pancreatic organoids can be used to generate insulin-producing beta cells for diabetic patients.

Get this: Last year, researchers at Vienna’s Institute of Molecular Biotechnology (IMB) coaxed human iPS cells derived from skin to develop into peppercorn-sized organoids similar to developing brains.

Scientists at Yokohama City University in Japan have also grown tiny liver “buds” from human iPS cells and transplanted them into mice, where they functioned like real human liver tissue. Others have grown and transplanted organoids that mimic the pancreas, intestines, eyes and kidneys.

Studies of how organs form when stem cells divide, mature and organize into 3-D structures led to the development of organoids as a research model in the late 2000s. Like any model, though, organoids are “really good for some things but not for others,” Wells says. Unlike a rodent, an organoid can’t model behavior or complex interactions with other organs, for example.

But a big opportunity remains: Organoids could be used to study developmental disorders, since researchers are essentially growing a new organ, which is what happens during development. IMB researchers discovered that the stem cells inside brain organoids derived from individuals with microcephaly — a condition in which a child’s head is small for their age and sex — matured too early, depleting the population of stem cells that fuel normal brain growth.

And then, there’s their most obvious function: spare parts. Grapin-Botton has grown pancreatic organoids from mouse embryonic stem cells; she’s now planning to grow them from human cells to generate insulin-producing beta cells for diabetic patients. And Christodoulos Xinaris at the Mario Negri Institute for Pharmacological Research has grown renal organoids mouse embryonic cells that could one day be made with human cells and engrafted to diseased kidneys. Xinaris’ organoids might not be able to replace an entire kidney, but he thinks they could help a patient avoid dialysis by replacing the “broken” part.

Researchers hesitate to predict when these real-world applications could hit prime time. But Xinaris notes, “Right now, things are growing very fast.”

Just one more case where going big is all about going small.

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Meet The Author Melissa Pandika

Melissa Pandika is a lab rat-turned-journalist with eye to all things science, medicine and more. Like? Distance running, snails, late-night Korean BBQ + R&B slow jams.

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