Researchers Create Artificial Organs That Fit In Your Hand
Great balls of cells! Scientists are developing mock human organs that can fit in the palm of your hand.
These organs-on-a-chip are designed to test drugs and help understand the basics of how organs function when they are healthy and when they are diseased.
For instance, you have your gut-on-a-chip being developed at the Johns Hopkins School of Medicine. It's a high-tech approach to dealing with a scourge of the low-tech world.
"I'm interested in solving a worldwide problem of diarrheal diseases," says Dr. Mark Donowitz, who runs this lab. He says 800,000 children a year die from these diseases — notably cholera, rotavirus and certain strains of E. coli.
"We've failed so far to find drugs to treat diarrhea using cell culture models and mouse intestine," Donowitz says. Mice simply don't react the way we do to these germs, so they aren't very helpful for studying diseases of the gut.
The device that is being developed as a liver-on-a-chip and a kidney-on-a-chip.
So Donowitz's team is building what it hopes will be a much better way to study these diseases: the gut-on-a-chip. Truth be told, there's not a lot to see.
Postdoctoral researcher Jennifer Foulke-Abel holds one in the palm of her hand. It's a thin sheet of glass, topped with a plastic microscope slide and a tiny cavity inside. Half a dozen spaghetti-size tubes bristle from the device.
"The reason there are so many tubes is we have a vacuum chamber that will cause the membrane to stretch, the way the intestine stretches as it moves food along," Fouke-Abel explains.
Cells plucked from a human intestine will be put into a tiny chamber around that membrane, and they will divide, grow and even organize themselves much as you would find them in human guts. The device, when operating, might hold 50,000 gut cells.
Step 1 in this research is to see whether cells in the ersatz organ react the same way to diseases as do cells in the human gut.
"And in all three of the diseases I mentioned, we've been able to take that first step," Donowitz says. "So we know that these appear to be really good models of the human disease."
Still, it's a work in progress. The guts-on-a-chip produce digestive enzymes, hormones and mucus, but they don't yet incorporate other parts of the human intestine, such as blood vessels or nerve cells.
"They all have to be incorporated if you want to move from a simple to a more complex system, which I think you need to do if you are going to reproduce intestinal biology," Donowitz says.
This lab is moving in that direction. And once it has a complete system built, one use will be to test potential drugs for the diseases being studied. "We think this could be a real step forward in terms of reducing waste-of-time drug development," Donowitz says.
While this lab at Johns Hopkins is working to develop the gut, other labs scattered around the country are working on other organ systems.
This green blob is a cluster of gut cells that have organized themselves into a structure called an enteroid. In this time-lapse movie, you can see this blob gobbling up loose material, including a dead enteroid (dyed red). Enteroids act in some respects like miniature organs. Scientists use enteroids to build organs-on-a-chip.
"There's going to be a brain-on-a-chip, liver, heart and so on," says Danilo Tagle, who coordinates this overall effort at the National Center for Advancing Translational Sciences, which is part of the National Institutes of Health. It is funding development of 10 organ systems in all.
"The goal is actually to tie them in all together," Tagle says. So they will collectively act like an entire human being on a chip — at least from the point of view of a scientist interested in testing drugs. (The brain-on-a-chip will not think, of course.)
And Tagle says in the long run, scientists hope they can build many of these systems, each one based on the cells from an individual person. Imagine a small army of cell-based stand-ins for research.
"And so you can identify which part of the population might be more responsive to particular drugs, or identify a subset of the population that might be more vulnerable to the harmful effects of a particular drug," Tagle says.
He says this $75 million, five-year project took off thanks to pioneering work at the Wyss Institute for Biologically Inspired Engineering at Harvard. The research has been so promising, Wyss spun off a private company to pursue it.
"It's called Emulate," says Donald Ingber, founding director of the Wyss Institute. "It's just getting its feet on the ground. We have almost 20 people out of the Wyss Institute who are moving out with it."
Ingber says it would be too much to expect this technology to replace mice in medical research anytime soon. But he is hoping that this will speed up drug development and make it less expensive, "because if we can identify things that are more likely to work in humans, that's going to have major impact."
And there are so many avenues to pursue, he says, there's plenty of room for both industry and academics to work on building and improving these organs-on-a-chip.
9(MDE1MTIxMDg0MDE0MDQ3NTY3MzkzMzY1NA001))
Transcript
ROBERT SIEGEL, HOST:
And we're going to stick with science now. It's getting more difficult and more expensive to develop new drugs. And one reason is a lot of research depends on mice for testing, but people aren't simply big mice. So, to develop drugs faster, scientists want to grow simulated human organs in a lab. NPR's Richard Harris visited one lab that's working on that frontier.
RICHARD HARRIS, BYLINE: Dr. Mark Donowitz's lab at the Johns Hopkins Medical School is tapping into the high-tech worlds of bioengineering and cell biology to deal with a scourge of the low-tech world.
MARK DONOWITZ: I'm interested in solving a worldwide problem of diarrheal diseases that are still killing 800,000 children per year. And we've failed so far to develop drugs to treat diarrhea using cell culture models and mouse intestine.
HARRIS: So Donowitz's team is building what they hope will be a much better way to study cholera, rotavirus and deadly strains of E. coli. They're building miniature human guts on a device small enough to fit in the palm of your hand. Cells plucked from a human intestine are coaxed into dividing, growing and even organizing themselves much like you find them in human organs.
DONOWITZ: Our first part of this project is to show that what we know about the disease is reproduced. And, in all three of those diseases I mentioned, we've been able to take that first step. So we know that these appear to be really good models of the human disease.
HARRIS: Still, it's a work-in-progress. The guts on a chip produce digestive enzymes, hormones and mucus, but they don't yet incorporate other parts of the human intestines, such as blood vessels or nerve cells.
DONOWITZ: They all have to be incorporated if you really want to move from a simple to a more complex system, which I think you have to do to reproduce intestinal biology.
HARRIS: So how close are you to getting all of that packaged together?
DONOWITZ: This thing has just started 3 years ago.
HARRIS: It's early days, he says.
So, can I see one?
(LAUGHTER)
DONOWITZ: And off we go. OK.
HARRIS: We spend a few minutes looking at small packages made of glass and plastic, where the cells live. Postdoc Jennifer Foulke-Abel picks up a chip that bristles with tiny tubes.
JENNIFER FOULKE-ABEL: The reason that there's so many tubes is that we have a vacuum chamber that will cause the membrane to stretch in the same way that the intestine stretches as it moves food along.
HARRIS: Yes, even micro-guts work better with a bit of regularity. This particular chip would probably accommodate 50,000 gut cells, organized and working in concert, Donowitz says.
DONOWITZ: The biomedical engineers that work on this kind of thing talk in terms of micro-humans - one-millionth of a human.
HARRIS: So, could you take a drug and put it in this and see if the drug interferes with the disease?
DONOWITZ: Absolutely the idea. We think this could be a real step forward in reducing waste-of-time drug development.
HARRIS: And while Donowitz's lab is working to develop the gut, other labs scattered around the country are working on other organ systems.
DANILO TAGLE: There's going to be a brain on a chip, liver, heart and so on.
HARRIS: Danilo Tagle coordinates this overall effort at the National Center for Advancing Translational Sciences, which is part of the NIH. They're funding development of ten organ systems in all.
TAGLE: Their goal is actually to tie them in altogether.
HARRIS: So they collectively act like a entire human being on a chip, at least in some respects. And Tagle says, in the long run, they hope they can build many of these systems, each one based on the cells from an individual person. That way, you can not just study a disease in the abstract, but tailored to an individual or a subset of patients.
TAGLE: And so then you can identify which part of the population might be more responsive to particular drugs, or identify a subset of the population that might be more vulnerable to the harmful effects of a particular drug.
HARRIS: Tagle says this $75 million, five-year project was inspired by pioneering work in this area up at the Wyss Institute for Biologically Inspired Engineering at Harvard. Dr. Donald Ingber is the institute's founding director, and he's been pushing this technology forward as fast as he can.
DONALD INGBER: The only way it's going to get to have real-world impact is for it to be commercialized.
HARRIS: And, to that end, the Wyss Institute spun off a chunk of its research on its organs-on-a-chip to a private company.
INGBER: It's called Emulate. It's just getting its feet on the ground. We have about almost 20 people out of the Wyss Institute that are moving out with it.
HARRIS: Ingber says it would be too much to expect this technology to replace mice in medical research anytime soon.
INGBER: What I am hoping to see is to shorten the timeline for drug development and hopefully decrease cost, because, if we can identify things that are more likely to work in humans, that's going to have major impact.
HARRIS: And there are so many avenues to pursue here. He says there's plenty of room for both industry and academics to work on building and improving these organs on a chip. Richard Harris, NPR News. Transcript provided by NPR, Copyright NPR.
300x250 Ad
300x250 Ad