This research attempted to bioengineer pancreatic islets so that once transplanted they not only produce insulin but also induce tolerance of the immune system to prevent rejection. Islets were bioengineered with a special protein that persisted on the surface of islets for >1 week in the lab. These bioengineered islets were then transplanted into diabetic mice and established normal blood glucose control indefinitely, demonstrating functionality and lack of acute toxicity. Most importantly, the transplantation of the bioengineered islets in conjunction with a short course of rapamycin treatment resulted in robust localized immune system tolerance in 100% of the mouse recipients. Tolerance was initiated and maintained by Regulatory T-cells, as their depletion early during tolerance induction or late after established tolerance resulted in prompt graft rejection. Furthermore, Regulatory T-cells collected from long-term transplant-recipient mice prevented the rejection of normal transplanted islets, further confirming the Regulatory T-cell role in establishing immune system tolerance.
Yolcu ES, Zhao H, Bandura-Morgan L, Lacelle C, Woodward KB, Askenasy N, Shirwan H. (2011). Pancreatic islets engineered with SA-FasL protein establish robust localized tolerance by inducing regulatory T cells in mice. J Immunol. Dec 1;187(11):5901-9. Epub 2011 Nov 7.
Ramifications for Individuals with Type 1 Diabetes:
Bioengineered islets may be useful in the designs of encapsulation technologies to protect transplanted islets without the use of chronic immunosuppression.
This study was funded in part by JDRF grants to Dr. Shirwan’s laboratory.