Some membrane configurations do not cover the entire islet surface. If even a small bit of the islet is uncovered, macrophages can infiltrate and destroy the entire islet . The cellular attack and destruction sensitize the immune system, leading to a humoral (antibody) response, which can then destroy even those cells that are completely covered. Thus, complete coverage of all of the islets is required to protect the islet cells from both cellular and humoral immune responses.
Destruction of islet with a few exposed cells
The cartoon shows cellular destruction of an islet. First immune cells appear (blue). Three cells protrude outside the right capsule. These immune cells (T cells, macrophages) rapidly identify the foreign islet cells, invade the islet through the hole in the capsule, and destroy the entire islet. The islet on the left is protected by its capsule.
Very few systems have been developed which ensure complete coverage of all islets. None can achieve complete coverage within the dimensional constraints imposed by oxygen requirement. Islet Sheet is the only technology which absolutely ensures complete coverage of every islet with a thin, precisely controlled depth of over-coating.
Destruction of an islet through the capsules when the immune system is sensitized
The required extent of exclusion of antibody and complement cannot be predicted. Complement-mediated cell death requires the cooperativity of many large molecules acting in concert. Complete exclusion of antibody and complement is likely to be unnecessary, and would also be deleterious to islet viability because of nutrient exclusion.
The cartoon shows humoral destruction of an islet following cellular destruction of an exposed islet. First immune cells appear (blue) that rapidly identify the foreign islet cells on the right capsule, invade the islet through the hole in the capsule, and destroy the entire islet. Meanwhile, a B cell begins making antibody (red). This combines with circulating complement to destroy the islet through the protecting capsule. Thus the islet on the left is destroyed in spite of its capsule.
By virtue of its retrievability, the Islet Sheet offers the unique ability to resolve the allowable exclusion limit of antibody and complement empirically. By retrieving the intact implant some time after implantation we can study the extent of immune rejection and islet starvation in a realistic and quantitative manner. No other coating technology under development allows complete retrieval of implanted islets, nor the exquisite control of permeability.