Skip to main content
Top
Published in: Current Diabetes Reports 3/2017

01-03-2017 | Immunology, Transplantation, and Regenerative Medicine (L Piemonti and V Sordi, Section Editors)

Porcine Islet Xenografts: a Clinical Source of ß-Cell Grafts

Authors: Bassem F. Salama, Gregory S. Korbutt

Published in: Current Diabetes Reports | Issue 3/2017

Login to get access

Abstract

Purpose of Review

Diabetes is medical and social burden affecting millions around the world. Despite intensive therapy, insulin fails to maintain adequate glucose homeostasis and often results in episodes of hypoglycemic unawareness. Islet transplantation is a propitious replacement therapy, and incremental improvements in islet isolation and immunosuppressive drugs have made this procedure a feasible option. Shortage of donors, graft loss, and toxic immunosuppressive agents are few of many hurdles against making human allogenic islet transplantation a routine procedure.

Recent Findings

Xenografts—especially pig islets—offer a logical alternative source for islets. Current preclinical studies have revealed problems such as optimal islet source, zoonosis, and immune rejection. These issues are slowing clinical application.

Summary

Genetically modified pigs, encapsulation devices, and new immune-suppressive regimens can confer graft protection. In addition, extrahepatic transplant sites are showing promising results. Notwithstanding few approved clinical human trials, and available data from non-human primates, recent reports indicate that porcine islets are closer to be the promising solution to cure diabetes.
Literature
1.
2.
go back to reference International Diabetes Federation. IDF diabetes atlas—7th edition. IDF 2015. International Diabetes Federation. IDF diabetes atlas—7th edition. IDF 2015.
4.
go back to reference Da Rocha Fernandes J, Ogurtsova K, Linnenkamp U, Guariguata L, Seuring T, Zhang P. Diabetes Atlas estimates of 2014 global health expenditures on diabetes. Diabetes Res Clin Pract. 2014;2016(117):48–54. doi:10.1016/j.diabres.2016.04.016. Da Rocha Fernandes J, Ogurtsova K, Linnenkamp U, Guariguata L, Seuring T, Zhang P. Diabetes Atlas estimates of 2014 global health expenditures on diabetes. Diabetes Res Clin Pract. 2014;2016(117):48–54. doi:10.​1016/​j.​diabres.​2016.​04.​016.
10.
go back to reference • Dholakia S, Oskrochi Y, Easton G, Papalois V. Advances in pancreas transplantation. J R Soc Med. 2016;109:141–6. doi:10.1177/0141076816636369. This review is very informative and demonstrates history and recent advances in pancreas transplantation.CrossRefPubMed • Dholakia S, Oskrochi Y, Easton G, Papalois V. Advances in pancreas transplantation. J R Soc Med. 2016;109:141–6. doi:10.​1177/​0141076816636369​. This review is very informative and demonstrates history and recent advances in pancreas transplantation.CrossRefPubMed
11.
go back to reference Brendel M, Hering B, Schulz A, Bretzel R. International Islet Transplant Registry report #8. Germany, University of Giessen. 1999: 1–20. Brendel M, Hering B, Schulz A, Bretzel R. International Islet Transplant Registry report #8. Germany, University of Giessen. 1999: 1–20.
12.
go back to reference Warnock GL, Kneteman NM, Ryan E, Seelis RE, Rabinovitch A, Rajotte RV. Normoglycaemia after transplantation of freshly isolated and cryopreserved pancreatic islets in type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1991;34:55–8. doi:10.1007/BF00404026.CrossRefPubMed Warnock GL, Kneteman NM, Ryan E, Seelis RE, Rabinovitch A, Rajotte RV. Normoglycaemia after transplantation of freshly isolated and cryopreserved pancreatic islets in type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1991;34:55–8. doi:10.​1007/​BF00404026.CrossRefPubMed
13.
go back to reference Warnock GL, Kneteman NM, Ryan EA, Rabinovitch A, Rajotte RV. Long-term follow-up after transplantation of insulin-producing pancreatic islets into patients with type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1992;35:89–95. doi:10.1007/BF00400857.CrossRefPubMed Warnock GL, Kneteman NM, Ryan EA, Rabinovitch A, Rajotte RV. Long-term follow-up after transplantation of insulin-producing pancreatic islets into patients with type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1992;35:89–95. doi:10.​1007/​BF00400857.CrossRefPubMed
14.
15.
go back to reference Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000;343:230–8. doi:10.1056/NEJM200007273430401.CrossRefPubMed Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000;343:230–8. doi:10.​1056/​NEJM200007273430​401.CrossRefPubMed
19.
go back to reference Shapiro AM, Ricordi C, Hering BJ, Auchincloss H, Lindblad R, Robertson RP, et al. International trial of the Edmonton protocol for islet transplantation. N Engl J Med. 2006;355:1318–30. doi:10.1056/NEJMoa061267.CrossRefPubMed Shapiro AM, Ricordi C, Hering BJ, Auchincloss H, Lindblad R, Robertson RP, et al. International trial of the Edmonton protocol for islet transplantation. N Engl J Med. 2006;355:1318–30. doi:10.​1056/​NEJMoa061267.CrossRefPubMed
20.
go back to reference Warnock GL, Meloche RM, Thompson D, Shapiro RJ, Fung M, Ao Z, et al. Improved human pancreatic islet isolation for a prospective cohort study of islet transplantation vs best medical therapy in type 1 diabetes mellitus. Arch Surg. 2005;140:735–44. doi:10.1001/archsurg.140.8.735.CrossRefPubMed Warnock GL, Meloche RM, Thompson D, Shapiro RJ, Fung M, Ao Z, et al. Improved human pancreatic islet isolation for a prospective cohort study of islet transplantation vs best medical therapy in type 1 diabetes mellitus. Arch Surg. 2005;140:735–44. doi:10.​1001/​archsurg.​140.​8.​735.CrossRefPubMed
21.
go back to reference Hering BJ, Clarke WR, Bridges ND, Eggerman TL, Alejandro R, Bellin MD, et al. Phase 3 trial of transplantation of human islets in type 1 diabetes complicated by severe hypoglycemia. Diabetes Care. 2016;39:1230–40. doi:10.2337/dc15-1988.CrossRefPubMed Hering BJ, Clarke WR, Bridges ND, Eggerman TL, Alejandro R, Bellin MD, et al. Phase 3 trial of transplantation of human islets in type 1 diabetes complicated by severe hypoglycemia. Diabetes Care. 2016;39:1230–40. doi:10.​2337/​dc15-1988.CrossRefPubMed
22.
go back to reference Brennan DC, Kopetskie HA, Sayre PH, Alejandro R, Cagliero E, Shapiro AMJ, et al. Long-term follow-up of the Edmonton protocol of islet transplantation in the United States. Am J Transplant. 2016;16:509–17. doi:10.1111/ajt.13458.CrossRefPubMed Brennan DC, Kopetskie HA, Sayre PH, Alejandro R, Cagliero E, Shapiro AMJ, et al. Long-term follow-up of the Edmonton protocol of islet transplantation in the United States. Am J Transplant. 2016;16:509–17. doi:10.​1111/​ajt.​13458.CrossRefPubMed
23.
go back to reference World Health Organization. Statement from the xenotransplantation advisory consultation. 2005. World Health Organization. Statement from the xenotransplantation advisory consultation. 2005.
27.
go back to reference Wong BS, Yamada K, Okumi M, Weiner J, O’Malley PE, Tseng YL, et al. Allosensitization does not increase the risk of xenoreactivity to alpha1,3-galactosyltransferase gene-knockout miniature swine in patients on transplantation waiting lists. Transplantation. 2006;82:314–9. doi:10.1097/01.tp.0000228907.12073.0b.CrossRefPubMed Wong BS, Yamada K, Okumi M, Weiner J, O’Malley PE, Tseng YL, et al. Allosensitization does not increase the risk of xenoreactivity to alpha1,3-galactosyltransferase gene-knockout miniature swine in patients on transplantation waiting lists. Transplantation. 2006;82:314–9. doi:10.​1097/​01.​tp.​0000228907.​12073.​0b.CrossRefPubMed
29.
30.
31.
go back to reference Hering BJ, Wijkstrom M, Graham ML, Hårdstedt M, Aasheim TC, Jie T, et al. Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates. Nat Med. 2006;12:301–3. doi:10.1038/nm1369.CrossRefPubMed Hering BJ, Wijkstrom M, Graham ML, Hårdstedt M, Aasheim TC, Jie T, et al. Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates. Nat Med. 2006;12:301–3. doi:10.​1038/​nm1369.CrossRefPubMed
32.
go back to reference Jin SM, Lee HS, Oh SH, Park HJ, Park JB, Kim JH, et al. Adult porcine islet isolation using a ductal preservation method and purification with a density gradient composed of histidine-tryptophan-ketoglutarate solution and iodixanol. Transplant Proc. 2014;46:1628–32. doi:10.1016/j.transproceed.2014.03.004.CrossRefPubMed Jin SM, Lee HS, Oh SH, Park HJ, Park JB, Kim JH, et al. Adult porcine islet isolation using a ductal preservation method and purification with a density gradient composed of histidine-tryptophan-ketoglutarate solution and iodixanol. Transplant Proc. 2014;46:1628–32. doi:10.​1016/​j.​transproceed.​2014.​03.​004.CrossRefPubMed
33.
go back to reference Shin JS, Kim JM, Kim JS, Min BH, Kim YH, Kim HJ, et al. Long-term control of diabetes in immunosuppressed nonhuman primates (NHP) by the transplantation of adult porcine islets. Am J Transplant. 2015;15:2837–50. doi:10.1111/ajt.13345.CrossRefPubMed Shin JS, Kim JM, Kim JS, Min BH, Kim YH, Kim HJ, et al. Long-term control of diabetes in immunosuppressed nonhuman primates (NHP) by the transplantation of adult porcine islets. Am J Transplant. 2015;15:2837–50. doi:10.​1111/​ajt.​13345.CrossRefPubMed
36.
go back to reference Cardona K, Pearson TC, Korbutt GS, Lyon J, Milas Z, Rajotte RV, et al. Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways. Nat Med. 2006;12:304–6. doi:10.1038/nm1375.CrossRefPubMed Cardona K, Pearson TC, Korbutt GS, Lyon J, Milas Z, Rajotte RV, et al. Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways. Nat Med. 2006;12:304–6. doi:10.​1038/​nm1375.CrossRefPubMed
42.
go back to reference Arefanian H, Tredget EB, Rajotte RV, Gill RG, Korbutt GS, Rayat GR. Short-term administrations of a combination of anti-LFA-1 and anti-CD154 monoclonal antibodies induce tolerance to neonatal porcine islet xenografts in mice. Diabetes. 2010;59:958–66. doi:10.2337/db09-0413.CrossRefPubMedPubMedCentral Arefanian H, Tredget EB, Rajotte RV, Gill RG, Korbutt GS, Rayat GR. Short-term administrations of a combination of anti-LFA-1 and anti-CD154 monoclonal antibodies induce tolerance to neonatal porcine islet xenografts in mice. Diabetes. 2010;59:958–66. doi:10.​2337/​db09-0413.CrossRefPubMedPubMedCentral
45.
47.
go back to reference Elliott RB. Microencapsulated neonatal porcine islet implants alleviate unaware hypoglycaemia without immune suppression. In communication to 23th World Congress of IPITA. Prague, Czech Republic. 2011. Elliott RB. Microencapsulated neonatal porcine islet implants alleviate unaware hypoglycaemia without immune suppression. In communication to 23th World Congress of IPITA. Prague, Czech Republic. 2011.
49.
go back to reference Bennet W, Groth C, Larsson R, Nilsson B, Korsgren O. Isolated human islets trigger an instant blood mediated inflammatory reaction: implications for intraportal islet transplantation as a treatment for patients with type 1 diabetes. Ups J Med Sci. 2000;105:125–33. doi:10.1517/03009734000000059.CrossRefPubMed Bennet W, Groth C, Larsson R, Nilsson B, Korsgren O. Isolated human islets trigger an instant blood mediated inflammatory reaction: implications for intraportal islet transplantation as a treatment for patients with type 1 diabetes. Ups J Med Sci. 2000;105:125–33. doi:10.​1517/​0300973400000005​9.CrossRefPubMed
50.
go back to reference Moberg L, Johansson H, Lukinius A, Berne C, Foss A, Källen R, et al. Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation. Lancet. 2002;360:2039–45. doi:10.1016/S0140-6736(02)12020-4.CrossRefPubMed Moberg L, Johansson H, Lukinius A, Berne C, Foss A, Källen R, et al. Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation. Lancet. 2002;360:2039–45. doi:10.​1016/​S0140-6736(02)12020-4.CrossRefPubMed
54.
go back to reference Ozmen L, Ekdahl KN, Elgue G, Larsson R, Korsgren O, Nilsson B. Inhibition of thrombin abrogates the instant blood-mediated inflammatory reaction triggered by isolated human islets: possible application of the thrombin inhibitor melagatran in clinical islet transplantation. Diabetes. 2002;51:1779–84. doi:10.2337/diabetes.51.6.1779.CrossRefPubMed Ozmen L, Ekdahl KN, Elgue G, Larsson R, Korsgren O, Nilsson B. Inhibition of thrombin abrogates the instant blood-mediated inflammatory reaction triggered by isolated human islets: possible application of the thrombin inhibitor melagatran in clinical islet transplantation. Diabetes. 2002;51:1779–84. doi:10.​2337/​diabetes.​51.​6.​1779.CrossRefPubMed
56.
go back to reference Ricordi C, Socci C, Davalli AM, Staudacher C, Baro P, Vertova A, et al. Isolation of the elusive pig islet. Surgery. 1990;107:688.PubMed Ricordi C, Socci C, Davalli AM, Staudacher C, Baro P, Vertova A, et al. Isolation of the elusive pig islet. Surgery. 1990;107:688.PubMed
59.
go back to reference • Krishnan R, Buder B, Alexander M, Foster CE, Lakey JR. Juvenile porcine islets can restore euglycemia in diabetic athymic nude mice after xenotransplantation. Transplantation. 2015;99:710–6. doi:10.1097/TP.0000000000000667. A great recent report regarding the juvenile porcine islets and their potential benefits.CrossRefPubMed • Krishnan R, Buder B, Alexander M, Foster CE, Lakey JR. Juvenile porcine islets can restore euglycemia in diabetic athymic nude mice after xenotransplantation. Transplantation. 2015;99:710–6. doi:10.​1097/​TP.​0000000000000667​. A great recent report regarding the juvenile porcine islets and their potential benefits.CrossRefPubMed
60.
go back to reference Mueller KR, Balamurugan AN, Cline GW, Pongratz RL, Hooper RL, Weegman BP, et al. Differences in glucose-stimulated insulin secretion in vitro of islets from human, nonhuman primate, and porcine origin. Xenotransplantation. 2013;20:75–81. doi:10.1111/xen.12022.CrossRefPubMedPubMedCentral Mueller KR, Balamurugan AN, Cline GW, Pongratz RL, Hooper RL, Weegman BP, et al. Differences in glucose-stimulated insulin secretion in vitro of islets from human, nonhuman primate, and porcine origin. Xenotransplantation. 2013;20:75–81. doi:10.​1111/​xen.​12022.CrossRefPubMedPubMedCentral
61.
65.
66.
go back to reference Vériter S, Gianello P, Igarashi Y, Beaurin G, Ghyselinck A, Aouassar N, et al. Improvement of subcutaneous bioartificial pancreas vascularization and function by coencapsulation of pig islets and mesenchymal stem cells in primates. Cell Transplant. 2014;23:1349–64. doi:10.3727/096368913X663550.CrossRefPubMed Vériter S, Gianello P, Igarashi Y, Beaurin G, Ghyselinck A, Aouassar N, et al. Improvement of subcutaneous bioartificial pancreas vascularization and function by coencapsulation of pig islets and mesenchymal stem cells in primates. Cell Transplant. 2014;23:1349–64. doi:10.​3727/​096368913X663550​.CrossRefPubMed
72.
go back to reference Bennet W, Bjorkland A, Sundberg B, Davies H, Liu J, Holgersson J, et al. A comparison of fetal and adult porcine islets with regard to gal (1, 3) gal expression and the role of human immunoglobulins and complement in islet cell cytotoxicity. Transplantation. 2000;69:1711–7.CrossRefPubMed Bennet W, Bjorkland A, Sundberg B, Davies H, Liu J, Holgersson J, et al. A comparison of fetal and adult porcine islets with regard to gal (1, 3) gal expression and the role of human immunoglobulins and complement in islet cell cytotoxicity. Transplantation. 2000;69:1711–7.CrossRefPubMed
75.
go back to reference World Health Organization. Second WHO global consultation on regulatory requirements for xenotransplantation clinical trials. WHO 2011. World Health Organization. Second WHO global consultation on regulatory requirements for xenotransplantation clinical trials. WHO 2011.
76.
go back to reference Takeuchi Y, Patience C, Magre S, Weiss RA, Banerjee PT, Tissier PL, et al. Host range and interference studies of three classes of pig endogenous retrovirus. J Virol. 1998;72:9986–91.PubMedPubMedCentral Takeuchi Y, Patience C, Magre S, Weiss RA, Banerjee PT, Tissier PL, et al. Host range and interference studies of three classes of pig endogenous retrovirus. J Virol. 1998;72:9986–91.PubMedPubMedCentral
77.
go back to reference Patience C, Takeuchi Y, Weiss RA. Infection of human cells by an endogenous retrovirus of pigs. Nat Med. 1997;3:282–6.CrossRefPubMed Patience C, Takeuchi Y, Weiss RA. Infection of human cells by an endogenous retrovirus of pigs. Nat Med. 1997;3:282–6.CrossRefPubMed
79.
go back to reference Valdes-Gonzalez RA, Dorantes LM, Garibay GN, Bracho-Blanchet E, Mendez AJ, Davila-Perez R, et al. Xenotransplantation of porcine neonatal islets of Langerhans and Sertoli cells: a 4-year study. Eur J Endocrinol 2005:153:419–27. DOI: 153/3/419. Valdes-Gonzalez RA, Dorantes LM, Garibay GN, Bracho-Blanchet E, Mendez AJ, Davila-Perez R, et al. Xenotransplantation of porcine neonatal islets of Langerhans and Sertoli cells: a 4-year study. Eur J Endocrinol 2005:153:419–27. DOI: 153/3/419.
81.
go back to reference Valdes-Gonzalez R, Dorantes LM, Bracho-Blanchet E, Rodríguez-Ventura A, White DJG. No evidence of porcine endogenous retrovirus in patients with type 1 diabetes after long-term porcine islet xenotransplantation. J Med Virol. 2010;82:331–4. doi:10.1002/jmv.21655.CrossRefPubMed Valdes-Gonzalez R, Dorantes LM, Bracho-Blanchet E, Rodríguez-Ventura A, White DJG. No evidence of porcine endogenous retrovirus in patients with type 1 diabetes after long-term porcine islet xenotransplantation. J Med Virol. 2010;82:331–4. doi:10.​1002/​jmv.​21655.CrossRefPubMed
82.
85.
go back to reference Gala-Lopez BL, Pepper AR, Pawlick RL, O’Gorman D, Kin T, Bruni A, et al. Antiaging glycopeptide protects human islets against tacrolimus-related injury and facilitates engraftment in mice. Diabetes. 2016;65:451–62. doi:10.2337/db15-0764.CrossRefPubMed Gala-Lopez BL, Pepper AR, Pawlick RL, O’Gorman D, Kin T, Bruni A, et al. Antiaging glycopeptide protects human islets against tacrolimus-related injury and facilitates engraftment in mice. Diabetes. 2016;65:451–62. doi:10.​2337/​db15-0764.CrossRefPubMed
88.
go back to reference Kumagai-Braesch M, Jacobson S, Mori H, Jia X, Takahashi T, Wernerson A, et al. The TheraCyte™ device protects against islet allograft rejection in immunized hosts. Cell Transplant. 2013:22:1137. doi: 0.3727/096368912X657486. Kumagai-Braesch M, Jacobson S, Mori H, Jia X, Takahashi T, Wernerson A, et al. The TheraCyte™ device protects against islet allograft rejection in immunized hosts. Cell Transplant. 2013:22:1137. doi: 0.3727/096368912X657486.
92.
go back to reference Korbutt GS, Elliott JF, Ao Z, Flashner M, Warnock GL, Rajotte RV. Microencapsulation of neonatal porcine islets: long-term reversal of diabetes in nude mice and in vitro protection from human complement mediated cytolysis. Transplant Proc. 1997;29:2128. doi:10.1016/S0041-1345(97)00259-5.CrossRefPubMed Korbutt GS, Elliott JF, Ao Z, Flashner M, Warnock GL, Rajotte RV. Microencapsulation of neonatal porcine islets: long-term reversal of diabetes in nude mice and in vitro protection from human complement mediated cytolysis. Transplant Proc. 1997;29:2128. doi:10.​1016/​S0041-1345(97)00259-5.CrossRefPubMed
93.
go back to reference Rayat GR, Rajotte RV, Ao Z, Korbutt GS. Microencapsulation of neonatal porcine islets: protection from human antibody/complement-mediated cytolysis in vitro and long-term reversal of diabetes in nude mice. Transplantation. 2000;69:1084–90.CrossRefPubMed Rayat GR, Rajotte RV, Ao Z, Korbutt GS. Microencapsulation of neonatal porcine islets: protection from human antibody/complement-mediated cytolysis in vitro and long-term reversal of diabetes in nude mice. Transplantation. 2000;69:1084–90.CrossRefPubMed
94.
95.
96.
go back to reference • Veiseh O, Doloff JC, Ma M, Vegas AJ, Tam HH, Bader AR, et al. Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates. Nat Mater. 2015;14:643–51. doi:10.1038/nmat4290. An interesting report debating the old concept of minimizing the capsule size to increase oxygen diffusion.CrossRefPubMedPubMedCentral • Veiseh O, Doloff JC, Ma M, Vegas AJ, Tam HH, Bader AR, et al. Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates. Nat Mater. 2015;14:643–51. doi:10.​1038/​nmat4290. An interesting report debating the old concept of minimizing the capsule size to increase oxygen diffusion.CrossRefPubMedPubMedCentral
99.
go back to reference Markmann JF, Rosen M, Siegelman ES, Soulen MC, Deng S, Barker CF, et al. Magnetic resonance-defined periportal steatosis following intraportal islet transplantation: a functional footprint of islet graft survival? Diabetes. 2003;52:1591–4. doi:10.2337/diabetes.52.7.1591.CrossRefPubMed Markmann JF, Rosen M, Siegelman ES, Soulen MC, Deng S, Barker CF, et al. Magnetic resonance-defined periportal steatosis following intraportal islet transplantation: a functional footprint of islet graft survival? Diabetes. 2003;52:1591–4. doi:10.​2337/​diabetes.​52.​7.​1591.CrossRefPubMed
100.
102.
103.
go back to reference Sionov RV, Finesilver G, Sapozhnikov L, Soroker A, Zlotkin-Rivkin E, Saad Y, et al. Beta cells secrete significant and regulated levels of insulin for long periods when seeded onto acellular micro-scaffolds. Tissue Eng A. 2015;21:2691–702. doi:10.1089/ten.tea.2014.0711.CrossRef Sionov RV, Finesilver G, Sapozhnikov L, Soroker A, Zlotkin-Rivkin E, Saad Y, et al. Beta cells secrete significant and regulated levels of insulin for long periods when seeded onto acellular micro-scaffolds. Tissue Eng A. 2015;21:2691–702. doi:10.​1089/​ten.​tea.​2014.​0711.CrossRef
107.
go back to reference Pepper AR, Gala-Lopez B, Pawlick R, Merani S, Kin T, Shapiro AMJ. A prevascularized subcutaneous device-less site for islet and cellular transplantation. Nat Biotechnol. 2015;33:518–23. doi:10.1038/nbt.3211.CrossRefPubMed Pepper AR, Gala-Lopez B, Pawlick R, Merani S, Kin T, Shapiro AMJ. A prevascularized subcutaneous device-less site for islet and cellular transplantation. Nat Biotechnol. 2015;33:518–23. doi:10.​1038/​nbt.​3211.CrossRefPubMed
108.
Metadata
Title
Porcine Islet Xenografts: a Clinical Source of ß-Cell Grafts
Authors
Bassem F. Salama
Gregory S. Korbutt
Publication date
01-03-2017
Publisher
Springer US
Published in
Current Diabetes Reports / Issue 3/2017
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-017-0846-7

Other articles of this Issue 3/2017

Current Diabetes Reports 3/2017 Go to the issue

Microvascular Complications—Nephropathy (M Afkarian, Section Editor)

The Role of Endoplasmic Reticulum Stress in Diabetic Nephropathy

Diabetes Epidemiology (NM Maruthur, Section Editor)

Arsenic Exposure and Type 2 Diabetes: MicroRNAs as Mechanistic Links?

Microvascular Complications—Nephropathy (M Afkarian, Section Editor)

Caveolin-1 in the Pathogenesis of Diabetic Nephropathy: Potential Therapeutic Target?

Microvascular Complications—Nephropathy (M Afkarian, Section Editor)

Diet and Diabetic Kidney Disease: Plant Versus Animal Protein

Microvascular Complications—Nephropathy (M Afkarian, Section Editor)

Intestinal Microbiota in Type 2 Diabetes and Chronic Kidney Disease