Use of Magnetocapsules for in Vivo Visualization and Enhanced Survival of Xenogeneic HepG2 Cell Transplants

Abstract

Hepatocyte transplantation is currently being considered as a new paradigm for treatment of fulminant liver failure. Xeno- and allotransplantation studies have shown considerable success, but the long-term survival and immunorejection of engrafted cells need to be further evaluated. Using novel alginate–protamine sulfate–alginate microcapsules, we have coencapsulated luciferase-expressing HepG2 human hepatocytes with superparamagnetic iron oxide nanoparticles to create magnetocapsules that are visible on MRI as discrete hypointensities. Magnetoencapsulated cells survive and secrete albumin for at least 5 weeks in vitro. When transplanted intraperitoneally in immunocompetent mice, encapsulated hepatocytes survive for at least 4 weeks as determined using bioluminescent imaging, which is in stark contrast to naked, unencapsulated hepatocytes that died within several days after transplantation. However, in vivo human albumin secretion did not follow the time course of magnetoencapsulated cell survival, with plasma levels returning to baseline values already at 1 week post-transplantation. The present results demonstrate that encapsulation can dramatically prolong survival of xenotransplanted hepatocytes, leading to sustained albumin secretion with a duration that may be long enough for use as a temporary therapeutic bridge to liver transplantation.