Implanting insulin-producing beta cells that are protected from the immune attack is a promising approach to restoring insulin independence in individuals with T1D. Human islet cells either non-encapsulated or alginate-encapsulated were implanted under the kidney or in the peritoneal cavity of diabetic mice and in the peritoneal cavity of one person with T1D. Implants were followed for function and were retrieved for analysis of cellular composition and insulin secretory responsiveness. Non-encapsulated implants with low beta cell purity were non-functional and underwent 90% beta cell loss. At medium purity, they were functional at post-transplant week 1, and controlled glucose levels in half the mice but had no effect in the other half depending on the degree of beta cell-specific losses. Encapsulated implants immediately and sustainably corrected diabetes, irrespective of beta cell purity in all of the mice. Most of the capsules were retrievable as single units from the mice and were enriched in endocrine cells that exhibited rapid secretory responses to glucose and glucagon. Single capsules with similar properties were also retrieved from a person with T1D at post-transplant month 3. However, the vast majority of capsules were broken and contained debris, explaining the poor rise in C-peptide levels in this person. In summary, In immunodeficient mice, intraperitoneal-implanted, alginate-encapsulated human islet cells exhibited a better outcome than free implants placed under the kidney. Retrieved capsules exhibited secretory responses to glucose, which was also observed in a human T1D recipient.
Ramifications for Individuals with T1D:
Alginate is one of the most studied and a promising material for islet encapsulation. This study helps to explain how these alginate capsules affect the islets over time after implantation. These findings will help researchers understand how to improve alginate-based encapsulation designs to move this approach a step closer to becoming a viable human therapy for T1D.
This study was funded in part by JDRF.
Investigators and Institutions:
This study was conducted by Dr. Daniel Pipeleers and his colleagues at the Brussels Free University.
Jacobs-Tulleneers-Thevissen D, Chintinne M, and others. Sustained function of alginate-encapsulated human islet cell implants in the peritoneal cavity of mice leading to a pilot study in a type 1 diabetic patient. Diabetologia. 2013 Jul;56(7):1605-14. Epub 2013 Apr 26.