Longitudinal Studies on the Microcirculation around the TheraCyte™ Immunoisolation Device, Using the Laser Doppler Technique

Abstract

Encapsulation of cellular grafts in an immunoisolation membrane device may make it possible to perform transplantation without having to give immunosuppressive drugs. A common problem is the development of an avascular fibrotic zone around the implants, leading to impaired graft survival. The TheraCyte™ macroencapsulation device has therefore been designed to facilitate neovascularization of the device's surface. In this study, we evaluated the microcirculation around empty TheraCyte™ devices implanted SC in rats at various times after implantation, using a laser Doppler probe introduced via the device port. Studies were performed on day 1 or at 1, 2, and 4 weeks or at 2, 3, and 12 months after implantation. The mean flow was 158 ± 42, 148 ± 50, 133 ± 28, 72 ± 17, 138 ± 41, 165 ± 43, and 160 ± 29 perfusion units (PU), respectively. Thus, the microcirculation around the device was significantly reduced at 4 weeks after implantation (p < 0.01) while, from 2 months onwards the circulation had improved and did not differ significantly from that on day 1. The present study shows time-related changes in the microcirculatory flow around TheraCyte™ macroencapsulation devices that agree with our previous microdialysis studies on in vivo exchange of insulin and glucose between the device and the circulation. Laser Doppler flowmetry seems to provide a reliable technique for screening blood perfusion around macroencapsulation devices.