“Living drug factories” might treat diabetes and other diseases

Chemical engineers have developed a way to protect transplanted drug-producing cells from immune system rejection.

Implantable living drug factories could treat diabetes and other diseases
Xinhua/Mohamed Khidir via Getty Images
One promising way to treat diabetes is with transplanted islet cells that produce insulin when blood sugar levels get too high.

However, patients who receive such transplants must take drugs to prevent their immune systems from rejecting the transplanted cells, so the treatment is not often used.

To help make this type of therapy more feasible, MIT researchers have now devised a way to encapsulate therapeutic cells in a flexible protective device that prevents immune rejection while still allowing oxygen and other critical nutrients to reach the cells. Such cells could pump out insulin or other proteins whenever they are needed.

"The vision is to have a living drug factory that you can implant in patients, which could secrete drugs as-needed in the patient. We hope that technology like this could be used to treat many different diseases, including diabetes," says Daniel Anderson, an associate professor of chemical engineering, a member of MIT's Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science, and the senior author of the work.

In a study of mice, the researchers showed that genetically engineered human cells remained viable for at least five months, and they believe they could last longer to achieve long-term treatment of chronic diseases such as diabetes or hemophilia, among others.

Suman Bose, a research scientist at the Koch Institute, is the lead author of the paper, which appears today in Nature Biomedical Engineering.

Protective effect

Patients with type 1 diabetes usually have to inject themselves with insulin several times a day to keep their blood sugar levels within a healthy range. Since 1999, a small number of diabetes patients have received transplanted islet cells, which can take over for their nonfunctioning pancreas. While the treatment is often effective, the immunosuppressant drugs that these patients have to take make them vulnerable to infection and can have other serious side effects.

For several years, Anderson's lab has been working on ways to protect transplanted cells from the host's immune system, so that immunosuppressant drugs would not be necessary.

"We want to be able to implant cells into patients that can secrete therapeutic factors like insulin, but prevent them from being rejected by the body," Anderson says. "If you could build a device that could protect those cells and not require immune suppression, you could really help a lot of people."

To protect the transplanted cells from the immune system, the researchers housed them inside a device built out of a silicon-based elastomer (polydimethylsiloxane) and a special porous membrane. "It's almost the same stiffness as tissue, and you make it thin enough so that it can wrap around organs," Bose says.

They then coated the outer surface of the device with a small-molecule drug called THPT. In a previous study, the researchers had discovered that this molecule can help prevent fibrosis, a buildup of scar tissue that results when the immune system attacks foreign objects.

The device contains a porous membrane that allows the transplanted cells obtain nutrients and oxygen from the bloodstream. These pores must be large enough to allow nutrients and insulin to pass through, but small enough so that immune cells such as T cells can't get in and attack the transplanted cells.

In this study, the researchers tested polymer coatings with pores ranging from 400 nanometers to 3 micrometers in diameter, and found that a size range of 800 nanometers to 1 micrometer was optimal. At this size, small molecules and oxygen can pass through, but not T cells. Until now, it had been believed that 1-micrometer pores would be too large to stop cellular rejection.

Drugs on demand

In a study of diabetic mice, the researchers showed that transplanted rat islets inside microdevices maintained normal blood glucose levels in the mice for more than 10 weeks.

The researchers also tested this approach with human embryonic kidney cells that were engineered to produce erythropoietin (EPO), a hormone that promotes red blood cell production and is used to treat anemia. These therapeutic human cells survived in mice for at least the 19-week duration of the experiment.

"The cells in the device act as a factory and continuously produce high levels of EPO. This led to an increase in the red blood cell count in the animals for as long as we did the experiment," Anderson says.

In addition, the researchers showed that they could program the transplanted cells to produce a protein only in response to treatment with a small molecule drug. Specifically, the transplanted engineered cells produced EPO when mice were given the drug doxycycline. This strategy could allow for on-demand production of a protein or hormone only when it is needed.

This type of "living drug factory" could be useful for treating any kind of chronic disease that requires frequent doses of a protein or hormone, the researchers say. They are currently focusing on diabetes and are working on ways to extend the lifetime of transplanted islet cells.

"This is the eighth Nature journal paper our team has published in the past four-plus years elucidating key fundamental aspects of biocompatibility of implants. We hope and believe these findings will lead to new super-biocompatible implants to treat diabetes and many other diseases in the years to come," says Robert Langer, the David H. Koch Institute Professor at MIT and an author of the paper.

Sigilon Therapeutics, a company founded by Anderson and Langer, has patented the use of the THPT coating for implantable devices and is now developing treatments based on this approach.

The research was funded by JDRF. Other authors of the paper include Lisa Volpatti, Devina Thiono, Volkan Yesilyurt, Collin McGladian, Yaoyu Tang, Amanda Facklam, Amy Wang, Siddharth Jhunjhunwala, Omid Veiseh, Jennifer Hollister-Lock, Chandrabali Bhattacharya, Gordon Weir, and Dale Greiner.

Reprinted with permission of MIT News. Read the original article.

What does kindness look like? It wears a mask.

Northwell Health CEO Michael Dowling has an important favor to ask of the American people.

Sponsored by Northwell Health
  • Michael Dowling is president and CEO of Northwell Health, the largest health care system in New York state. In this PSA, speaking as someone whose company has seen more COVID-19 patients than any other in the country, Dowling implores Americans to wear masks—not only for their own health, but for the health of those around them.
  • The CDC reports that there have been close to 7.9 million cases of coronavirus reported in the United States since January. Around 216,000 people have died from the virus so far with hundreds more added to the tally every day. Several labs around the world are working on solutions, but there is currently no vaccine for COVID-19.
  • The most basic thing that everyone can do to help slow the spread is to practice social distancing, wash your hands, and to wear a mask. The CDC recommends that everyone ages two and up wear a mask that is two or more layers of material and that covers the nose, mouth, and chin. Gaiters and face shields have been shown to be less effective at blocking droplets. Homemade face coverings are acceptable, but wearers should make sure they are constructed out of the proper materials and that they are washed between uses. Wearing a mask is the most important thing you can do to save lives in your community.
Keep reading Show less

Science confirms: Earth has more than one 'moon'

Two massive clouds of dust in orbit around the Earth have been discussed for years and finally proven to exist.

J. Sliz-Balogh, A. Barta and G. Horvath
Surprising Science
  • Hungarian astronomers have proven the existence of two "pseudo-satellites" in orbit around the earth.
  • These dust clouds were first discovered in the sixties, but are so difficult to spot that scientists have debated their existence since then.
  • The findings may be used to decide where to put satellites in the future and will have to be considered when interplanetary space missions are undertaken.
Keep reading Show less

How do pandemics end? History suggests diseases fade but are almost never truly gone

Instead of looking forward, we should be consulting the past.

Andrew Redington/Getty Images
Coronavirus

When will the pandemic end? All these months in, with over 37 million COVID-19 cases and more than 1 million deaths globally, you may be wondering, with increasing exasperation, how long this will continue.

Keep reading Show less

Scientists stumble across new organs in the human head

New cancer-scanning technology reveals a previously unknown detail of human anatomy.

Credit: Valstar et al., Netherlands Cancer Institute
Surprising Science
  • Scientists using new scanning technology and hunting for prostate tumors get a surprise.
  • Behind the nasopharynx is a set of salivary glands that no one knew about.
  • Finding the glands may allow for more complication-free radiation therapies.
Keep reading Show less
Personal Growth

Millennials reconsidering finances and future under COVID-19

A new survey found that 27 percent of millennials are saving more money due to the pandemic, but most can't stay within their budgets.

Scroll down to load more…
Quantcast