The TheraCyte™ Device Protects against Islet Allograft Rejection in Immunized Hosts

Cell Transplantation

Article

Stella Jacobson¹  Malin Flodström-Tullberg¹  Annika Wernerson²  Hiroki Mori³  Xiaohui Jia³  Makiko Kumagai-Braesch³  Annika Tibell³  Tohru Takahashi³ 

[1] Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden;Division of Renal Medicine, CLINTEC, Karolinska Institutet, Stockholm, Sweden;Division of Transplantation Surgery, CLINTEC, Karolinska Institutet, Stockholm, Sweden;

关键词: Islet transplantation;    Immunized recipients;    TheraCyte™ device;    Macroencapsulation;    Alloantibodies;    IFN-γ ELISpot;   

DOI  :  10.3727/096368912X657486

 received in 2010-11-11, accepted in 2012-06-03,  发布年份 2013

来源: Sage Journals

【 摘 要 】

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.

【 授权许可】

Unknown   
© 2013 Cognizant Comm. Corp.

【 图 表 】

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