Each of 6 patients with T1DM and problematic hypoglycemia received 2 islet transplants into pre-implanted Sernova Cell Pouches (SCPs). Each procedure involved transplantation of islets into two 8-channel SCPs and one mini sentinel SCP. SCP implants and the combination of SCP with human cadaveric islets are both well tolerated with durations exceeding 3 years. Detectable islet function (≥0.3ng/ml peak serum c-peptide in mixed meal tolerance test) was achieved in 4 patients following islet transplant to SCP. It was correlated with transplanted islet mass of 300k-500k IEQ per procedure. Transplantation of islet mass <300k IEQ did not lead to detectable c-peptide secretion. C-peptide was detectable for periods ranging from days up to 12 months after the procedure. Three patients with suboptimal levels of immunosuppression due to non-compliance experienced antibody mediated rejection based on de novo donor specific antibodies (DSAs). One patient with DSAs had detectable stimulated c-peptide at 90 days post-transplant. Histological assessment of sentinel SCPs retrieved ≥90 days post-transplant revealed surviving functional islets within vascularized SCP channels via positive immunofluorescence staining of insulin, c-peptide, glucagon and somatostatin in 5 of 6 patients. Five patients received supplemental intraportal islet transplants (IPITx) and all of them remain insulin independent (>2.5Y, >1Y, 10M, 2M, 1M). The sixth patient is awaiting an IPITx in the coming months as per protocol. Safety and dose-response observations from the first cohort of 6 patients led to the implementation of 10-channel SCPs with 50% greater transplant capacity than the 8-channel configuration in a second study cohort. Two additional patients were recently implanted with 10-channel SCPs and are currently awaiting their first islet transplantation.

Disclosure

M.Ogledzinski: None. L.Wang: None. M.Tibudan: None. R.Barth: None. J.Fung: None. P.Witkowski: Advisory Panel; Vertex Pharmaceuticals Incorporated, Novartis. S.Gondek: None. W.Lin: None. K.Milejczyk: None. B.Juengel: None. L.Potter: None. P.J.Bachul: None. L.Basto: None. L.Perea: None.

Funding

Sernova; JDRF

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.