The TheraCyte™ Device Protects against Islet Allograft Rejection in Immunized Hosts
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 Th...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2013-07-01
|
| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368912X657486 |
| _version_ | 1818043010512846848 |
|---|---|
| author | Makiko Kumagai-Braesch Stella Jacobson Hiroki Mori Xiaohui Jia Tohru Takahashi Annika Wernerson Malin Flodström-Tullberg Annika Tibell |
| author_facet | Makiko Kumagai-Braesch Stella Jacobson Hiroki Mori Xiaohui Jia Tohru Takahashi Annika Wernerson Malin Flodström-Tullberg Annika Tibell |
| author_sort | Makiko Kumagai-Braesch |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T08:55:25Z |
| format | Article |
| id | doaj.art-d3b7a17271fb4a18bc33d85565ba2315 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-10T08:55:25Z |
| publishDate | 2013-07-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-d3b7a17271fb4a18bc33d85565ba23152022-12-22T01:55:27ZengSAGE PublishingCell Transplantation0963-68971555-38922013-07-012210.3727/096368912X657486The TheraCyte™ Device Protects against Islet Allograft Rejection in Immunized HostsMakiko Kumagai-Braesch0Stella Jacobson1Hiroki Mori2Xiaohui Jia3Tohru Takahashi4Annika Wernerson5Malin Flodström-Tullberg6Annika Tibell7Division of Transplantation Surgery, CLINTEC, Karolinska Institutet, Stockholm, SwedenCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, SwedenDivision of Transplantation Surgery, CLINTEC, Karolinska Institutet, Stockholm, SwedenDivision of Transplantation Surgery, CLINTEC, Karolinska Institutet, Stockholm, SwedenDivision of Transplantation Surgery, CLINTEC, Karolinska Institutet, Stockholm, SwedenDivision of Renal Medicine, CLINTEC, Karolinska Institutet, Stockholm, SwedenCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, SwedenDivision of Transplantation Surgery, CLINTEC, Karolinska Institutet, Stockholm, SwedenClinically, 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.https://doi.org/10.3727/096368912X657486 |
| spellingShingle | Makiko Kumagai-Braesch Stella Jacobson Hiroki Mori Xiaohui Jia Tohru Takahashi Annika Wernerson Malin Flodström-Tullberg Annika Tibell The TheraCyte™ Device Protects against Islet Allograft Rejection in Immunized Hosts Cell Transplantation |
| title | The TheraCyte™ Device Protects against Islet Allograft Rejection in Immunized Hosts |
| title_full | The TheraCyte™ Device Protects against Islet Allograft Rejection in Immunized Hosts |
| title_fullStr | The TheraCyte™ Device Protects against Islet Allograft Rejection in Immunized Hosts |
| title_full_unstemmed | The TheraCyte™ Device Protects against Islet Allograft Rejection in Immunized Hosts |
| title_short | The TheraCyte™ Device Protects against Islet Allograft Rejection in Immunized Hosts |
| title_sort | theracyte™ device protects against islet allograft rejection in immunized hosts |
| url | https://doi.org/10.3727/096368912X657486 |
| work_keys_str_mv | AT makikokumagaibraesch thetheracytedeviceprotectsagainstisletallograftrejectioninimmunizedhosts AT stellajacobson thetheracytedeviceprotectsagainstisletallograftrejectioninimmunizedhosts AT hirokimori thetheracytedeviceprotectsagainstisletallograftrejectioninimmunizedhosts AT xiaohuijia thetheracytedeviceprotectsagainstisletallograftrejectioninimmunizedhosts AT tohrutakahashi thetheracytedeviceprotectsagainstisletallograftrejectioninimmunizedhosts AT annikawernerson thetheracytedeviceprotectsagainstisletallograftrejectioninimmunizedhosts AT malinflodstromtullberg thetheracytedeviceprotectsagainstisletallograftrejectioninimmunizedhosts AT annikatibell thetheracytedeviceprotectsagainstisletallograftrejectioninimmunizedhosts AT makikokumagaibraesch theracytedeviceprotectsagainstisletallograftrejectioninimmunizedhosts AT stellajacobson theracytedeviceprotectsagainstisletallograftrejectioninimmunizedhosts AT hirokimori theracytedeviceprotectsagainstisletallograftrejectioninimmunizedhosts AT xiaohuijia theracytedeviceprotectsagainstisletallograftrejectioninimmunizedhosts AT tohrutakahashi theracytedeviceprotectsagainstisletallograftrejectioninimmunizedhosts AT annikawernerson theracytedeviceprotectsagainstisletallograftrejectioninimmunizedhosts AT malinflodstromtullberg theracytedeviceprotectsagainstisletallograftrejectioninimmunizedhosts AT annikatibell theracytedeviceprotectsagainstisletallograftrejectioninimmunizedhosts |