Surface Modification of Islets With L-DOPA–KF7 Enhances Islet Survival by Inhibiting IBMIR in Intrahepatic Islet Transplantation

This is the authors' abstract. We don't add key points for this paper.

Intrahepatic islet transplantation is followed by islet loss due to the instant blood-mediated inflammatory response (IBMIR) in which platelet activation plays a key role. The KEATSTF-fragment (KF7), a newly discovered platelet inhibitor that interferes with the formation of the 14-3-3ζ-c-Src-integrin-β3 complex, holds significant potential in inhibiting IBMIR without causing significant bleeding. This study introduces a novel surface modification technique using 3,4-dihydroxy-l-phenylalanine (L-DOPA) conjugated with KF7 to enhance the engraftment of transplanted islets in a syngeneic marginal mass model. KF7 loaded with L-DOPA (L-DOPA-KF7) formed a protective coating on the surface of islets without interfering with their viability and functionality. Islets coated with L-DOPA-KF7 restored normoglycemia in diabetic mice, and survival time was significantly longer compared with the control group. Transplantation of L-DOPA-KF7-coated islets was associated with reduced blood clot formation and decreased infiltration of CD11b+ cells and platelets. In conclusion, a composite L-DOPA-KF7 coating significantly prolongs the survival of transplanted islets by providing a robust IBMIR isolation barrier, thereby enhancing the overall success of islet transplantation in preclinical models. ARTICLE HIGHLIGHTS: KEATSTF-fragment (KF7), an inhibitor of 14-3-3ζ-c-Src-integrin-β3 complex, effectively suppresses the instant blood-mediated inflammatory response by reducing thrombosis without increasing the risk of bleeding. The dopamine precursor 3,4-dihydroxy-l-phenylalanine (L-DOPA) can simply bind to the surface of islets without affecting cell viability or functionality, thus providing potential opportunities for clinical applications. A composite L-DOPA-KF7 coating effectively inhibited infiltration of platelets and CD11+ cells, thereby enhancing the efficacy of islet transplantation.