MIT chemical engineers created a protective layer for drug-producing cells so they can be safely transplanted and avoid immune system rejection. The development could pave the way for a new type of implantable cell that could deliver drugs in vivo, which would be an attractive option for people with diseases such as diabetes. It would eliminate the need for regular injections to keep blood sugar levels in check. Instead, the transplanted cells would produce the hormone necessary from within the body.
Currently, some diabetic patients have the option of receiving transplanted islet cells that take on the role of a functioning pancreas. However, the treatment requires that the patient also take immunosuppressant drugs so the host’s immune system won’t attack and destroy the cells. Such drugs can have severe side effects and make the patient vulnerable to infection. That’s why the MIT team has been working for years on finding a way to protect the cells so that immunosuppressant drugs would not be necessary.
Daniel Anderson, a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science, an associate professor of chemical engineering, and the senior author of the study said:
“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. If you could build a device that could protect those cells and not require immune suppression, you could really help a lot of people.
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.”
The cells are encapsulated in a flexible shell built out of a silicon-based elastomer (polydimethylsiloxane) and a porous membrane with about the same stiffness as tissue. The pores are wide enough to allow oxygen, nutrients, and insulin to pass through, but small enough to keep T cells (killer immune cells) out.
The team conducted different experiments to test the viability of the device and the therapeutic cells within.
In one experiment, they implanted rat islet cells in protective shells into diabetic mice. The mice’s blood glucose levels remained normal for over ten weeks.
Another animal study involved transplanting human embryonic kidney cells that were engineered to produce erythropoietin (EPO) – a hormone that drives red blood cell production and is, therefore, used to treat anemia – in mice. The cells survived for over 19 weeks and even led to an increase in red blood cell count.
Anderson said:
“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.”
Next, the team tested if the encapsulated cell could be triggered to produce EPO only when activated to do so by certain drugs. They programmed cells to produce a protein only when triggered by a small molecule drug and transplanted the engineered cells into mice. Only when the animals were given the drug doxycycline did the cells produce EPO.
This final experiment is the closest strategy to an on-demand production of hormones and proteins, showing that the cells could serve as a sort of “living drug factory.” This type of treatment would be useful for managing chronic illnesses that require frequent doses of a hormone or protein.
Robert Langer, an MIT David H. Koch Institute Professor and an author of the paper, said:
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.
The team hopes the “living drug factory” technology could one day serve as a valuable tool to treat any kind of chronic disease. For now, the researchers are focusing on diabetes and extending the lifespan of the cells further.
