New technologies are now available that allow scientists to make mock human organs that can fit in the palm of your hand. These organs-on-a-chip can help test drugs and provide excellent model systems for organ function when they are healthy and when they are diseased.
Think of it: a gut-on-a-chip being developed at the Johns Hopkins School of Medicine can help determine if your heart medicine is actually causing your upset stomach or your diet. This type of technology is 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 and studies diarrheal diseases. According to Donowitz, 800,000 children a year die from diseases like 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. Unfortunately. mouse digestive systems don’t react the way human s do to these germs. Therefore, they aren’t very helpful for studying diseases of the gut. Therefore, Donowitz’s team is building his gut-on-a-chip technology in what he hopes will be a superior technique for studying these these diseases.
When you hold one of these devices in the palm of your hand, it is little more than a thin sheet of glass, topped with a plastic microscope slide with a tiny cavity inside. Half a dozen spaghetti-size tubes extend 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 isolated from a human intestine are placed into a tiny chamber around that membrane, and the cells divide, grow and organize themselves into a small version of part of a human gut. The device, when operating, might hold 50,000 gut cells.
The first step of this research is to determine if the cells in the chip react the same way to diseases as 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.”
To date, 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.
However, Donowitz’s laboratory is moving in that direction. Once it has built a complete system, they will use it 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 the Donowitz lab at Johns Hopkins is working to develop the gut, other labs scattered around the country are working on other organ systems.
“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. The grant structure for this study section will fund the development of 10 organ systems in all.
“The goal is actually to tie them in all together,” Tagle says. To this end, the mini-organs on a chip will collectively work together, much like an entire human being on a chip.
Tagle’s hope is that scientists can build many of these systems, each one based on the cells from an individual person. This would create an array of cell-based stand-ins for research or even diagnoses.
“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.
According to Tagle, 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.