Smart cells wear protection

A drug-coated membrane has been shown to protect transplanted islet cells from T-cell attack, negating the need for immunosuppression, in a murine model.

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A drug-coated membrane has been shown to protect transplanted islet cells from T-cell attack, negating the need for immunosuppression, in a murine model.

Researchers from MIT's Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (both MA, USA) have developed a method of protecting transplanted cells from the immune system in a murine model, preventing fibrosis and avoiding the need for immunosuppression prior to and post-transplantation. 

Transplanted pancreatic islet cells have been shown to take over from a nonfunctioning pancreas; however, the necessary immunosuppressant drugs administered to protect the transplanted cells can leave patients vulnerable to infection.

“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,” explained Daniel Anderson, Associate Professor of Chemical Engineering, Koch Institute for Integrative Cancer Research, and the senior author of the work. “If you could build a device that could protect those cells and not require immune suppression, you could really help a lot of people.”

In the study, published in Nature Biomedical Engineering, Anderson and the team were developing a ‘living drug factory’ to treat type 1 diabetes, involving transplanted pancreatic islet cells encapsulated within a polydimethylsiloxane device and wrapped in a porous membrane. The membrane’s optimal pore size was engineered to allow small molecules and oxygen through, but prevent T-cells, and was found to be between 800nm-1μm.

The whole device was then coated with a small molecule called THBT, which has previously been shown to prevent fibrosis. Researchers tested the device by implanting human embryonic kidney cells that had been engineered to produce erythropoietin (EPO). The cells survived for at least 19 weeks following implantation into a murine model and could also be programmed to release EPO on-demand, following the administration of doxycycline.

“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,” commented Robert Langer, the David H. Koch Institute Professor at MIT and an author of the paper.

Sources: Bose S, Volpatti LR, Thiono D et al. A retrievable implant for the long-term encapsulation and survival of therapeutic xenogeneic cells. Nat. Biomed. Eng. doi: 10.1038/s41551-020-0538-5 (2020) (Epub ahead of print);

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