title: The TheraCyte™ device protects against islet allograft rejection in immunized hosts.
abstract: Clinically, many candidates for islet transplantation are already immunized, which increases their risk of graft rejection. Encapsulation of pancreatic islets using the TheraCyte™ device has been shown to protect against allograft rejection in nonimmunized recipients. However, the capacity of the TheraCyte™ device to prevent rejection in immunized recipients has not yet been studied. In this study, the protective capacity of the TheraCyte™ device was evaluated in an allogeneic rat model. Lewis rats were used as islet donors, and nonimmunized (control) and alloimmunized, diabetic Wistar-Furth (WF) rats were used as recipients. Graft survival was shorter in immunized recipients than in nonimmunized recipients (mean survival, 5.3 ± 2.7 and 9.3 ± 1.6 days, respectively, p < 0.01) when nonencapsulated islets were transplanted under the kidney capsule. When islets were transplanted into the TheraCyte™ device, graft function was maintained during the 6-month study period in both immunized and nonimmunized rats. In oral glucose tolerance tests performed at 1 month after transplantation, both groups had similar insulin and blood glucose levels indicating similar metabolic functions. Volume densities and absolute volumes of tissue inside the devices 6 months after transplantation were also comparable between the two groups, indicating that both groups maintained similar amounts of endocrine tissue. A higher number of IFN-γ-producing CD8+ T-cells were detected in immunized WF rats compared to control WF rats transplanted with encapsulated islets. This suggests that donor-specific alloreactivity in recipient rats was sustained throughout the study period. This study suggests that the TheraCyte™ device protects islet allografts also in immunized recipients. Our results further highlight the potential for using macroencapsulation to avoid immunosuppressive therapy in clinical islet transplantation.
authors.affiliation: Division of Transplantation Surgery, CLINTEC, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. makiko.kumagai-braesch@ki.se
authors.forename: Makiko
authors.initials: M
authors.lastname: Kumagai-Braesch
authors.forename: Stella
authors.initials: S
authors.lastname: Jacobson
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mori
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Jia
authors.forename: Tohru
authors.initials: T
authors.lastname: Takahashi
authors.forename: Annika
authors.initials: A
authors.lastname: Wernerson
authors.forename: Malin
authors.initials: M
authors.lastname: Flodström-Tullberg
authors.forename: Annika
authors.initials: A
authors.lastname: Tibell
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000601:surgery; D005260:Female; D005951:Glucose Tolerance Test; D006084:Graft Rejection / Q000276:immunology*; D007328:Insulin / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology; D016381:Islets of Langerhans Transplantation / Q000276:immunology; D007518:Isoantibodies / Q000276:immunology / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D014184:Transplantation, Homologous / Q000295:instrumentation*
chemical_list: D007328:Insulin; D007518:Isoantibodies; D007371:Interferon-gamma