Date: 2nd April 2020
Article in brief:
Immune system rejection is a common occurrence with organ transplants. Similarly, cell transplants could also alleviate diseases such as diabetes, however, due to the transplanted cells requiring long-term systemic immune suppression this often inhibits their use. Now scientists have created a retrievable, protective implant to encapsulate therapeutic cells and prevent immune rejection.
Researchers from the Massachusetts Institute of Technology (MIT), US, led by Daniel Anderson synthesised an implant that could encapsulate therapeutic cells for transplantation. The implants consisted of a silicone reservoir and a porous polymeric membrane whose pore size was optimised so that it excluded host macrophages from entering, whilst enabling the flow of oxygen and nutrients to ensure viability of the transplanted cells. . Furthermore, for long-term functionality to be retained by the device a synthetic polymer coat was added. A small-molecule drug called THPT was conjugated to the coat, and was crucial to prevent fibrosis. This implant was then placed into the intraperitoneal space of immunocompetent mice.
Living drug factories
The team have an ongoing interest in diabetes, which proved to be a good test-bed for the device. They encapsulated pancreatic islets cells from rats in the device and implanted them into diabetic mice. The cells were able to sense and produce insulin in response to blood sugar levels and were able to restore normoglycaemia for a period >75 days.
The team also tested the device as a potential treatment for anaemia. They engineered human embryonic kidney cells to produce erythropoietin (EPO), a hormone that promotes red blood cell production. Once again the device was implanted into immunocompetent mice. These therapeutic human cells survived and continuously produced high levels of EPO which resulted in increased red blood cell counts. Furthermore, the team were able to introduce an inducible element to the system by engineering the cells to only produced EPO in response to a small molecule drug, doxycycline. The device supported the human cells for the duration of the experiment which was over four months.
Conclusions and future applications
This immune stealthy device offers real promise in the treatment of many diseases. The device, when combined with the relevant donor cells, is in effect is a living drug ‘factory’ able to supply frequent doses of protein or hormone to treat a wide range of chronic diseases. Here, the authors have demonstrated its potential to treat diabetes and anaemia but this is likely to be the tip of the iceberg of potential applications.
In fact, Daniel Anderson and fellow co-author of the paper Robert Langer, were founders of Sigilon Therapeutics in 2016. Sigilon, has patented the use of the THPT coating for implantable devices and is now developing treatments based on this approach. Their therapeutic focus is currently centred on rare blood disorders, diabetes and lysosomal storage disorders (LSD). They announced last month they had secured $80.3 million series B financing to advance their Shielded Living Therapeutics™ and are hoping to bring their first-in-human clinical trial for haemophilia A this year.
The success of the device in mice will hopefully translate into programmable, therapeutic delivery devices for the treatment of human disease without the need for immunosuppression.
For more information please see the press release from MIT
Bose, S., L. R. Volpatti, D. Thiono, V. Yesilyurt, C. McGladrigan, Y. Tang, A. Facklam, A. Wang, S. Jhunjhunwala, O. Veiseh, J. Hollister-Lock, C. Bhattacharya, G. C. Weir, D. L. Greiner, R. Langer and D. G. Anderson (2020). “A retrievable implant for the long-term encapsulation and survival of therapeutic xenogeneic cells.” Nature Biomedical Engineering.
https://doi.org/10.1038/s41551-020-0538-5
