Favorable outcome of experimental islet xenotransplantation without immunosuppression in a nonhuman primate model of diabetes

Barbara Ludwig; Stefan Ludwig; Anja Steffen; Yvonne Knauf; Baruch Zimerman; Sophie Heinke; Susann Lehmann; Undine Schubert; Janine Schmid; Martina Bleyer; Uwe Schönmann; Clark K. Colton; Ezio Bonifacio; Michele Solimena; Andreas Reichel; Andrew V. Schally; Avi Rotem; Uriel Barkai; Helena Grinberg-Rashi; Franz Josef Kaup; Yuval Avni; Peter Jones; Stefan R. Bornstein

doi:10.1073/pnas.1708420114

Favorable outcome of experimental islet xenotransplantation without immunosuppression in a nonhuman primate model of diabetes

Barbara Ludwig, Stefan Ludwig, Anja Steffen, Yvonne Knauf, Baruch Zimerman, Sophie Heinke, Susann Lehmann, Undine Schubert, Janine Schmid, Martina Bleyer, Uwe Schönmann, Clark K. Colton, Ezio Bonifacio, Michele Solimena, Andreas Reichel, Andrew V. Schally, Avi Rotem, Uriel Barkai, Helena Grinberg-Rashi, Franz Josef KaupYuval Avni, Peter Jones, Stefan R. Bornstein

Pathology

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Abstract

Transplantation of pancreatic islets for treating type 1 diabetes is restricted to patients with critical metabolic lability resulting from the need for immunosuppression and the shortage of donor organs. To overcome these barriers, we developed a strategy to macroencap-sulate islets from different sources that allow their survival and function without immunosuppression. Here we report successful and safe transplantation of porcine islets with a bioartificial pancreas device in diabetic primates without any immune suppression. This strategy should lead to pioneering clinical trials with xenotransplantation for treatment of diabetes and, thereby, represents a previously unidentified approach to efficient cell replacement for a broad spectrum of endocrine disorders and other organ dysfunctions.

Original language	English (US)
Pages (from-to)	11745-11750
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	114
Issue number	44
DOIs	https://doi.org/10.1073/pnas.1708420114
State	Published - Oct 31 2017

Keywords

Beta-cell replacement
Diabetes
Immune barrier
Porcine islets

ASJC Scopus subject areas

General

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10.1073/pnas.1708420114

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Ludwig, B., Ludwig, S., Steffen, A., Knauf, Y., Zimerman, B., Heinke, S., Lehmann, S., Schubert, U., Schmid, J., Bleyer, M., Schönmann, U., Colton, C. K., Bonifacio, E., Solimena, M., Reichel, A., Schally, A. V., Rotem, A., Barkai, U., Grinberg-Rashi, H., ... Bornstein, S. R. (2017). Favorable outcome of experimental islet xenotransplantation without immunosuppression in a nonhuman primate model of diabetes. Proceedings of the National Academy of Sciences of the United States of America, 114(44), 11745-11750. https://doi.org/10.1073/pnas.1708420114

Favorable outcome of experimental islet xenotransplantation without immunosuppression in a nonhuman primate model of diabetes. / Ludwig, Barbara; Ludwig, Stefan; Steffen, Anja; Knauf, Yvonne; Zimerman, Baruch; Heinke, Sophie; Lehmann, Susann; Schubert, Undine; Schmid, Janine; Bleyer, Martina; Schönmann, Uwe; Colton, Clark K.; Bonifacio, Ezio; Solimena, Michele; Reichel, Andreas; Schally, Andrew V.; Rotem, Avi; Barkai, Uriel; Grinberg-Rashi, Helena; Kaup, Franz Josef; Avni, Yuval; Jones, Peter; Bornstein, Stefan R.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 44, 31.10.2017, p. 11745-11750.

Research output: Contribution to journal › Article › peer-review

Ludwig, B, Ludwig, S, Steffen, A, Knauf, Y, Zimerman, B, Heinke, S, Lehmann, S, Schubert, U, Schmid, J, Bleyer, M, Schönmann, U, Colton, CK, Bonifacio, E, Solimena, M, Reichel, A, Schally, AV, Rotem, A, Barkai, U, Grinberg-Rashi, H, Kaup, FJ, Avni, Y, Jones, P & Bornstein, SR 2017, 'Favorable outcome of experimental islet xenotransplantation without immunosuppression in a nonhuman primate model of diabetes', Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 44, pp. 11745-11750. https://doi.org/10.1073/pnas.1708420114

Ludwig, Barbara ; Ludwig, Stefan ; Steffen, Anja ; Knauf, Yvonne ; Zimerman, Baruch ; Heinke, Sophie ; Lehmann, Susann ; Schubert, Undine ; Schmid, Janine ; Bleyer, Martina ; Schönmann, Uwe ; Colton, Clark K. ; Bonifacio, Ezio ; Solimena, Michele ; Reichel, Andreas ; Schally, Andrew V. ; Rotem, Avi ; Barkai, Uriel ; Grinberg-Rashi, Helena ; Kaup, Franz Josef ; Avni, Yuval ; Jones, Peter ; Bornstein, Stefan R. / Favorable outcome of experimental islet xenotransplantation without immunosuppression in a nonhuman primate model of diabetes. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 44. pp. 11745-11750.

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abstract = "Transplantation of pancreatic islets for treating type 1 diabetes is restricted to patients with critical metabolic lability resulting from the need for immunosuppression and the shortage of donor organs. To overcome these barriers, we developed a strategy to macroencap-sulate islets from different sources that allow their survival and function without immunosuppression. Here we report successful and safe transplantation of porcine islets with a bioartificial pancreas device in diabetic primates without any immune suppression. This strategy should lead to pioneering clinical trials with xenotransplantation for treatment of diabetes and, thereby, represents a previously unidentified approach to efficient cell replacement for a broad spectrum of endocrine disorders and other organ dysfunctions.",

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note = "Funding Information: ACKNOWLEDGMENTS. We thank the German Primate Center for highly professional support of the nonhuman primate studies. This study was supported by the Deutsche Forschungsgemeinschaft (DFG) Grant BR1179 (to B.L.) and Grants CRC/TRR 127 and 205 (to B.L. and S.R.B.), the German Ministry for Education and Research to the German Centre for Diabetes Research (DZD e.V.), and the DFG-Center for Regenerative Therapies Dresden, Germany. Publisher Copyright: {\textcopyright} 2017, National Academy of Sciences. All rights reserved.",

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AU - Zimerman, Baruch

AU - Heinke, Sophie

AU - Lehmann, Susann

AU - Schubert, Undine

AU - Schmid, Janine

AU - Bleyer, Martina

AU - Schönmann, Uwe

AU - Colton, Clark K.

AU - Bonifacio, Ezio

AU - Solimena, Michele

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AU - Rotem, Avi

AU - Barkai, Uriel

AU - Grinberg-Rashi, Helena

AU - Kaup, Franz Josef

AU - Avni, Yuval

AU - Jones, Peter

AU - Bornstein, Stefan R.

N1 - Funding Information: ACKNOWLEDGMENTS. We thank the German Primate Center for highly professional support of the nonhuman primate studies. This study was supported by the Deutsche Forschungsgemeinschaft (DFG) Grant BR1179 (to B.L.) and Grants CRC/TRR 127 and 205 (to B.L. and S.R.B.), the German Ministry for Education and Research to the German Centre for Diabetes Research (DZD e.V.), and the DFG-Center for Regenerative Therapies Dresden, Germany. Publisher Copyright: © 2017, National Academy of Sciences. All rights reserved.

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Favorable outcome of experimental islet xenotransplantation without immunosuppression in a nonhuman primate model of diabetes

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Keywords

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