Islet transplantation is an effective cure for T1D but the requirement for immunosuppression makes its application limited. AdoShell® is an implantable and fully retrievable scaffold for islet transplantation without immunosuppression. It is based on a permselective hydrogel film that allows the diffusion of insulin and prevents immune cell invasion. AdoShell® is a soft biomaterial with 95% water, synthetized from non-degradable polymers cross-linked by bio-orthogonal click chemistry. Encapsulated human islets displayed a gluco-responsive insulin secretion comparable to naked islets in perifusion experiments after 7 days and 1 month (N=3 donors 7 days / N=2 donors 1 month).
Wistar rat allogenic islets encapsulated in AdoShell® were implanted in immunocompetent STZ-induced diabetic rats. Insulin levels in vivo were on average 121pM/day over 41 days (n=22 rats), a significant increase versus negative control (45pM/day, n=9 rats) (M.W. t-test, p<0.0001). AdoShell® Islets led to physiological weight gain, reduction of fasting hyperglycemia, and sustained C-peptide and insulin secretion for over 6 months in diabetic rats. It was well tolerated and did not trigger inflammatory reaction nor fibrosis after the 6-month implantation period in rat peritoneal cavity. Neither biodegradation, nor immune cell penetration were observed.
A.Geissler: Employee; Adocia, Stock/Shareholder; Adocia. O.Jouannot: Employee; ADOCIA, Stock/Shareholder; ADOCIA. A.Gaffuri: Employee; ADOCIA, Stock/Shareholder; ADOCIA. C.Gautier: Employee; Centre européen d'étude du diabète, Biomeostasis, Charles Rivers Laboratories, Institut de recherche contre les cancers de l'appareil digestif, GenOway, NAMSA. Y.P.Courbebaisse: None. K.Bouzakri: Consultant; Adocia, Stock/Shareholder; ILONOV. R.Eloy: Stock/Shareholder; Adocia. O.Soula: Employee; Adocia, Stock/Shareholder; Adocia.
