Combination of Oxygen Delivery and Alginate Encapsulation Enabled Islet Transplantation Without Immunosuppression

This report describes the development of a novel macrochamber specially engineered for islet encapsulation. The subcutaneously implantable device allows for controlled and adequate oxygen supply and provides immunological protection of donor islets against the host immune system. The minimally invasive implantable chamber normalized blood glucose levels in diabetic rodents for up to 3 months. Pretreatment with a growth hormone-releasing hormone agonist significantly enhanced functioning of the implanted cells as shown by improving glucose tolerance and increasing beta cell insulin reserves in rats. This also allowed for a reduction of the islet mass required for metabolic control. As a result of hypervascularization of the tissue surrounding the device, no relevant delay in insulin response to glucose changes has been observed. Consequently, this system opens up a fundamental strategy for therapy of diabetes and may provide a promising avenue for future approaches to implantation of encapsulated beta cells.

Reference:

Ludwig B, Rotem A, Schmid J, Weir GC, Colton CK, Brendel MD, Neufeld T, Block NL, Yavriyants K, Steffen A, Ludwig S, Chavakis T, Reichel A, Azarov D, Zimermann B, Maimon S, Balyura M, Rozenshtein T, Shabtay N, Vardi P, Bloch K, de Vos P, Schally AV, Bornstein SR, Barkai U. (2012), Improvement of islet function in a bioartificial pancreas by enhanced oxygen supply and growth hormone releasing hormone agonist. Proc Natl Acad Sci U S A. Mar 27;109(13):5022-7.

Ramifications for Individuals with Type 1 Diabetes:

The unique design of this encapsulation device enables adequate oxygen supply and immune-protection of the islets. If successfully scaled up, it is a promising technology to enable long-term maintenance of implanted beta cells without chronic immunosuppression.

JDRF Involvement:

This work was not supported by JDRF.