One of the big problems with organ transplants and therapeutic cell treatments is that the body’s immune system sees them as unwelcome threats. To stop the immune system from attacking these foreign bodies, patients take immune suppressing drugs, which then leave them open to infections and disease. There may be a way, however, to protect foreign cells in the body from harm without the need for immune suppression, says Minglin Ma, Biological and Environmental Engineering. The Ma Group has created various types of biomaterials that can encapsulate disease-fighting cells for implantation into a patient’s body. The biomaterials then protect the cells from attack by the body’s immune system while at the same time allowing them to perform their therapeutic function.
Recently, Ma has focused on using his biomaterials to improve the delivery of insulin-producing cells to treat type 1 diabetes. Formally called juvenile diabetes, type 1 diabetes affects over a million Americans. It is an autoimmune disease in which the body’s immune system destroys the insulin-producing cells in the pancreas. It comes on suddenly, often in childhood, and results in a life-long dependence on insulin injections or pumps.
One of the most promising of Ma’s biomaterials for type 1 diabetes applications is called cellular thread. It is a biocompatible, mechanically strong, and easy-to-handle device. Inside the device, pancreatic islet cells that secrete insulin are protected from harm. “The biomaterial is like a window screen," says Ma. “It allows nutrients and oxygen to pass through to the islets and insulin to pass out to the host body, but it doesn’t let the body’s immune response get through to attack the foreign islets.”
The Ma lab is working on ways to make cellular thread clinically applicable. “We want to make it easy to implant and easy to take out,” Ma says. Together with James A. Flanders, Clinical Sciences, Ma is optimizing the cellular thread for implantation in the abdomen using a simple laparoscopic procedure.
“We develop different types of biomaterials for different purposes or to address different challenges,” Ma explains. “Sometimes we use nanofibers and sometimes we use hydrogels.”
The cellular thread research is funded by a three-year Hartwell Individual Biomedical Research Award given to Ma by the Hartwell Foundation, which supports biomedical research to advance children’s health. In addition, Ma has received funding from the American Diabetes Association and the Juvenile Diabetes Research Foundation, among others, to pursue other types of biomaterials and approaches for type 1 diabetes. “We develop different types of biomaterials for different purposes or to address different challenges,” Ma explains. “Sometimes we use nanofibers and sometimes we use hydrogels. It depends on our focus. With the cellular thread we want to deliver islets with an implanted device. But we are also looking at delivering cells derived from stem cells, instead of islets, and we are working on prevascularized and oxygen-enhanced devices, too.”
Hydrogels with Lots of Water
Ma is exploring another way to protect cells from immune-system attack by encapsulating them in high-water content hydrogels. “We want to make a hydrogel that has a lot of water in it because we think that the immune system’s response to it will be less,” Ma says. “Our bodies themselves have a high water content, so it’s possible a biomaterial made mostly of water will be less noticeable to the immune system. The cells we want to deliver with this material like higher water content as well, so it will be good for them, too.”
The challenge with a high-water content hydrogel lies in keeping the material strong. “We need a material that is robust—tough and resilient,” Ma says, “but the more water you have, the weaker the hydrogel.” The Ma group has seen promise in a hydrogel they’ve created that is 98 percent water and still can tolerate a high degree of stretching without tearing or breaking.
Hydrogels for Scaling up Organoid Production
With support from the National Institutes of Health, Ma is also addressing the need for engineered tissues for use in applications such as disease modeling and drug screening. The Ma Group has created a way to scale up the production of organoids—tiny, three-dimensional organ-buds grown in vitro that mimic many of the properties of the complete organ. Organoids can be grown in petri dishes, but it is extremely difficult to produce enough of them for industrial or clinical applications. “You can imagine if you want to do a drug screening, you need many organoids,” Ma says. “You can try to scale up with petri dishes, but it would be very labor intensive. Our method is automated. We can produce organoids on a much larger scale, much more easily.”
The researchers encapsulate individual small intestinal organoids in a micropackage of core-shell hydrogel. The inside layer of soft extracellular matrix provides structural and biochemical support to the organoid, while the outer layer of stiffer hydrogel forms a robust package that can be easily manipulated. They then put the cellular packages in a bioreactor where they can grow. “We can make thousands, millions, of these biopackages depending on the size of the bioreactor,” Ma says.
Ma has used the same technique to grow large quantities of breast mini tissue. He is working with Scott A. Coonrod, Baker Institute for Animal Health, and Charles G. Danko, Biomedical Sciences, to model breast cancer using the mini tissue. “We’ve just started this,” Ma says. “Eventually we’ll study how these mini tissues behave in different environments to see how breast cancer develops.”
Ma says he is pleased to use his expertise in chemical engineering with a materials focus to address agricultural and life science problems. “These are areas where you can make an impact,” he says. “You can help people, and I have a personal interest in that.”