Abstract
Diabetes mellitus is one of the most diffuse and destructive diseases. It affects more than 190 million individuals in the world and is the fifth leading killer of Americans, with 73,000 deaths every year. Diabetes is a disease in which the body’s failure to regulate glucose can lead to serious and even fatal complications. The incidence of diabetes has increased by 61% since 1991. The increasing prevalence and huge cost, exceeding 100 billion dollars annually in the United States, create the need for innovative research in this field [1]. There are two forms of diabetes, type I and type II, which differ in their pathogenesis. Type I is an autoimmune disease, presenting primarily during the first two decades of life and resulting from the destruction of insulin-producing β cells in the pancreatic islets of Langerhans. Type II generally presents in adults, is characterized by insulin resistance in the tissues and eventually β-cell failure in about 50% of the cases. In both types of diabetes the islets of Langerhans are the targets of destruction [2, 3].
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Hogan, P., T. Dall, and P. Nikolov. 2003. Economic costs of diabetes in the US in 2002. Diabetes Care 26:917–932
Calne, R. 2005. Cell transplantation for diabetes. Philos Trans R Soc Lond B Biol Sci 360:1769–1774
Peck, A.B., and V. Ramiya. 2004. In vitro-generation of surrogate islets from adult stem cells. Transpl Immunol 12:259–272
Kelly, W.D., R.C. Lillehei, F.K. Merkel, Y. Idezuki, and F.C. Goetz. 1967. Allotransplantation of the pancreas and duodenum along with the kidney in diabetic nephropathy. Surgery 61:827–837
CITR Coordinating Center CITR Annual Report 2007 NIH Bethesda, MD 2007
Najarian J, DER Sutherland and M. Steffes. 1975 Isolation of Human islets of Langerhans for Transplantation, Transplant Proc 7:611–13
Bretzel, R.G., H. Jahr, M. Eckhard, I. Martin, D. Winter, and M.D. Brendel. 2007. Islet cell transplantation today. Langenbecks Arch Surg 392:239–253
Ryan, E.A., J.R. Lakey, B.W. Paty, S. Imes, G.S. Korbutt, N.M. Kneteman, D. Bigam, R.V. Rajotte, and A.M. Shapiro. 2002. Successful islet transplantation: continued insulin reserve provides long-term glycemic control. Diabetes 51:2148–2157
Bromberg, J.S., B. Kaplan, P.F. Halloran, and R.P. Robertson. 2007. The islet transplant experiment: time for a reassessment. Am J Transplant 7:2217–2218
Ciubotariu, R., Z. Liu, A.I. Colovai, E. Ho, S. Itescu, S. Ravalli, M.A. Hardy, R. Cortesini, E.A. Rose, and N. Suciu-Foca. 1998. Persistent allopeptide reactivity and epitope spreading in chronic rejection of organ allografts. J Clin Invest 101:398–405
Vlad, G., R. Cortesini, and N. Suciu-Foca. 2005. License to heal: bidirectional interaction of antigen-specific regulatory T cells and tolerogenic APC. J Immunol 174:5907–5914
Inverardi, L., N.S. Kenyon, and C. Ricordi. 2003. Islet transplantation: immunological perspectives. Curr Opin Immunol 15:507–511
Klein, D., F. Barbe-Tuana, A. Pugliese, H. Ichii, D. Garza, M. Gonzalez, R.D. Molano, C. Ricordi, and R.L. Pastori. 2005. A functional CD40 receptor is expressed in pancreatic beta cells. Diabetologia 48:268–276
Molano, R.D., A. Pileggi, T. Berney, R. Poggioli, E. Zahr, R. Oliver, C. Ricordi, D.M. Rothstein, G.P. Basadonna, and L. Inverardi. 2003. Prolonged islet allograft survival in diabetic NOD mice by targeting CD45RB and CD154. Diabetes 52:957–964
Kenyon, N.S., M. Chatzipetrou, M. Masetti, A. Ranuncoli, M. Oliveira, J.L. Wagner, A.D. Kirk, D.M. Harlan, L.C. Burkly, and C. Ricordi. 1999. Long-term survival and function of intrahepatic islet allografts in rhesus monkeys treated with humanized anti-CD154. Proc Natl Acad Sci U S A 96:8132–8137
Berney, T., A. Pileggi, R.D. Molano, R. Poggioli, E. Zahr, C. Ricordi, and L. Inverardi. 2003. The effect of simultaneous CD154 and LFA-1 blockade on the survival of allogeneic islet grafts in nonobese diabetic mice. Transplantation 76:1669–1674
Molano, R.D., A. Pileggi, T. Berney, R. Poggioli, E. Zahr, R. Oliver, T.R. Malek, C. Ricordi, and L. Inverardi. 2003. Long-term islet allograft survival in nonobese diabetic mice treated with tacrolimus, rapamycin, and anti-interleukin-2 antibody. Transplantation 75:1812–1819
Gregori, S., P. Mangia, R. Bacchetta, E. Tresoldi, F. Kolbinger, C. Traversari, J.M. Carballido, J.E. de Vries, U. Korthauer, and M.G. Roncarolo. 2005. An anti-CD45RO/RB monoclonal antibody modulates T cell responses via induction of apoptosis and generation of regulatory T cells. J Exp Med 201:1293–1305
Gudjonsson, J.E., A. Johnston, M. Dyson, H. Valdimarsson, and J.T. Elder. 2007. Mouse models of psoriasis. J Invest Dermatol 127:1292–1308
Shultz, L.D., F. Ishikawa, and D.L. Greiner. 2007. Humanized mice in translational biomedical research. Nat Rev Immunol 7:118–130
Soria, B., E. Roche, G. Berna, T. Leon-Quinto, J.A. Reig, and F. Martin. 2000. Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes 49:157–162
Alexander, A.M., M. Crawford, S. Bertera, W.A. Rudert, O. Takikawa, P.D. Robbins, and M. Trucco. 2002. Indoleamine 2,3-dioxygenase expression in transplanted NOD Islets prolongs graft survival after adoptive transfer of diabetogenic splenocytes. Diabetes 51:356–365
Bertera, S., A.M. Alexander, M.L. Crawford, G. Papworth, S.C. Watkins, P.D. Robbins, and M. Trucco. 2004. Gene combination transfer to block autoimmune damage in transplanted islets of Langerhans. Exp Diabesity Res 5:201–210
Bertera, S., X. Gene, Z. Tawadrous, R. Bottino, A.N. Balanumrugan, W.A. Rudert, P. Drain, S.C. Watkins, M. Trucco. 2003. Body window-enabled in vivo multicolor imaging of transplanted mouse islets expressing an insulin-Timer fusion protein. Biotechniques 35:718–722
Rehman, K.K., S. Bertera, M. Trucco, A. Gambotto, and P.D. Robbins. 2007. Immunomodulation by adenoviral-mediated SCD40-Ig gene therapy for mouse allogeneic islet transplantation. Transplantation 84:301–307
Roche, E., J.A. Reig, A. Campos, B. Paredes, J.R. Isaac, S. Lim, R.Y. Calne, and B. Soria. 2005. Insulin-secreting cells derived from stem cells: clinical perspectives, hypes and hopes. Transpl Immunol 15:113–129
Shufaro, Y., and B.E. Reubinoff. 2004. Therapeutic applications of embryonic stem cells. Best Pract Res Clin Obstet Gynaecol 18:909–927
Koh, C.J., and A. Atala. 2004. Therapeutic cloning applications for organ transplantation. Transpl Immunol 12:193–201
Armstrong, L., and M. Lako. 2006. The future of human nuclear transfer? Stem Cell Rev 2:351–358
Takahashi, K., K. Tanabe, M. Ohnuki, M. Narita, T. Ichisaka, K. Tomoda, and S. Yamanaka. 2007. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872
Yu, J. M.A. Vodyanik, K. Smuga-Otto, J. Antosiewicz-Bourget, J.L. Frane, S. Tian, J. Nie, G.A. Jonsdottir, V. Ruotti, R. Stewart, I.I. Slukvin, and J.A. Thomson. 2007. Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920
Lock, L.T., and E.S. Tzanakakis. 2007. Stem/Progenitor cell sources of insulin-producing cells for the treatment of diabetes. Tissue Eng 13:1399–1412
Radvanyi, F., S. Christgau, S. Baekkeskov, C. Jolicoeur, and D. Hanahan. 1993. Pancreatic beta cells cultured from individual preneoplastic foci in a multistage tumorigenesis pathway: a potentially general technique for isolating physiologically representative cell lines. Mol Cell Biol 13:4223–4232
Kubo, S., H.K. Takahashi, M. Takei, H. Iwagaki, T. Yoshino, N. Tanaka, S. Mori, and M. Nishibori. 2004. E-prostanoid (EP)2/EP4 receptor-dependent maturation of human monocyte-derived dendritic cells and induction of helper T2 polarization. J Pharmacol Exp Ther 309:1213–1220
Yasunaga, M., S. Tada, S. Torikai-Nishikawa, Y. Nakano, M. Okada, L.M. Jakt, S. Nishikawa, T. Chiba, and T. Era. 2005. Induction and monitoring of definitive and visceral endoderm differentiation of mouse ES cells. Nat Biotechnol 23:1542–1550
D’Amour, K.A., A.D. Agulnick, S. Eliazer, O.G. Kelly, E. Kroon, and E.E. Baetge. 2005. Efficient differentiation of human embryonic stem cells to definitive endoderm. Nat Biotechnol 23:1534–1541
Falqui, L., S. Martinenghi, G.M. Severini, P. Corbella, M.V. Taglietti, C. Arcelloni, E. Sarugeri, L.D. Monti, R. Paroni, N. Dozio, G. Pozza, and C. Bordignon. 1999. Reversal of diabetes in mice by implantation of human fibroblasts genetically engineered to release mature human insulin. Hum Gene Ther 10:1753–1762
Cheung, A.T., B. Dayanandan, J.T. Lewis, G.S. Korbutt, R.V. Rajotte, M. Bryer-Ash, M.O. Boylan, M.M. Wolfe, and T.J. Kieffer. 2000. Glucose-dependent insulin release from genetically engineered K cells. Science 290:1959–1962
Yang, L., S. Li, H. Hatch, K. Ahrens, J.G. Cornelius, B.E. Petersen, and A.B. Peck. 2002. In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells. Proc Natl Acad Sci U S A 99:8078–8083
Peck, A.B., J.G. Cornelius, D. Schatz, and V.K. Ramiya. 2002. Generation of islets of Langerhans from adult pancreatic stem cells. J Hepatobiliary Pancreat Surg 9:704–709
Cornelius, J.G., V. Tchernev, K.J. Kao, and A.B. Peck. 1997. In vitro-generation of islets in long-term cultures of pluripotent stem cells from adult mouse pancreas. Horm Metab Res 29:271–277
Ramiya, V.K., M. Maraist, K.E. Arfors, D.A. Schatz, A.B. Peck, and J.G. Cornelius. 2000. Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nat Med 6:278–282
Bonner-Weir, S., M. Taneja, G.C. Weir, K. Tatarkiewicz, K.H. Song, A. Sharma, and J.J. O’Neil. 2000. In vitro cultivation of human islets from expanded ductal tissue. Proc Natl Acad Sci U S A 97:7999–8004
Hess, D., L. Li, M. Martin, S. Sakano, D. Hill, B. Strutt, S. Thyssen, D.A. Gray, and M. Bhatia. 2003. Bone marrow-derived stem cells initiate pancreatic regeneration. Nat Biotechnol 21:763–770
Mathews, V., P.T. Hanson, E. Ford, J. Fujita, K.S. Polonsky, and T.A. Graubert. 2004. Recruitment of bone marrow-derived endothelial cells to sites of pancreatic beta-cell injury. Diabetes 53:91–98
Zhao, Y., H. Wang, and T. Mazzone. 2006. Identification of stem cells from human umbilical cord blood with embryonic and hematopoietic characteristics. Exp Cell Res 312:2454–2464
Kodama, S., W. Kuhtreiber, S. Fujimura, E.A. Dale, and D.L. Faustman. 2003. Islet regeneration during the reversal of autoimmune diabetes in NOD mice. Science 302:1223–1227
Timper, K., D. Seboek, M. Eberhardt, P. Linscheid, M. Christ-Crain, U. Keller, B. Muller, and H. Zulewski. 2006. Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells. Biochem Biophys Res Commun 341:1135–1140
Hisatomi, Y., K. Okumura, K. Nakamura, S. Matsumoto, A. Satoh, K. Nagano, T. Yamamoto, and F. Endo. 2004. Flow cytometric isolation of endodermal progenitors from mouse salivary gland differentiate into hepatic and pancreatic lineages. Hepatology 39:667–675
Hori, Y., X. Gu, X. Xie, and S.K. Kim. 2005. Differentiation of insulin-producing cells from human neural progenitor cells. PLoS Med 2:e103
Colton, C.K. 1995. Implantable biohybrid artificial organs. Cell Transplant 4:415–436
Ryan, E.A., D. Bigam, and A.M. Shapiro. 2006. Current indications for pancreas or islet transplant. Diabetes Obes Metab 8:1–7
Calafiore, R. 1997. Perspectives in pancreatic and islet cell transplantation for the therapy of IDDM. Diabetes Care 20:889–896
Valdes-Gonzalez, R.A., L.M. Dorantes, G.N. Garibay, E. Bracho-Blanchet, A.J. Mendez, R. Davila-Perez, R.B. Elliott, L. Teran, and D.J. White. 2005. Xenotransplantation of porcine neonatal islets of Langerhans and Sertoli cells: a 4-year study. Eur J Endocrinol 153:419–427
Mendez, A.J., L. Inverardi, C. Ricordi, and N.S. Kenyon. 2007. The Miami results on porcine islet-Sertoli cell xenotransplantation. Xenotransplantation 14:89
Toso, C., Z. Mathe, P. Morel, J. Oberholzer, D. Bosco, D. Sainz-Vidal, D. Hunkeler, L.H. Buhler, C. Wandrey, and T. Berney. 2005. Effect of microcapsule composition and short-term immunosuppression on intraportal biocompatibility. Cell Transplant 14:159–167
Basta, G., P. Sarchielli, G. Luca, L. Racanicchi, C. Nastruzzi, L. Guido, F. Mancuso, G. Macchiarulo, G. Calabrese, P. Brunetti, and R. Calafiore. 2004. Optimized parameters for microencapsulation of pancreatic islet cells: an in vitro study clueing on islet graft immunoprotection in type 1 diabetes mellitus. Transpl Immunol 13:289–296
Orive, G., R.M. Hernandez, A.R. Gascon, R. Calafiore, T.M. Chang, P. De Vos, G. Hortelano, D. Hunkeler, I. Lacik, A.M. Shapiro, and J.L. Pedraz. 2003. Cell encapsulation: promise and progress. Nat Med 9:104–107
Desai, T.A., W.H. Chu, G. Rasi, P. Sinibaldi-Vallebona, E. Guarino, and M. Ferrari. 1999. Microfabricated biocapsules provide short-term immunoisolation of insulinoma xenografts. Biomed Microdevices 1:131–138
Duvivier-Kali, V.F., A. Omer, R.J. Parent, J.J. O’Neil, and G.C. Weir. 2001. Complete protection of islets against allorejection and autoimmunity by a simple barium-alginate membrane. Diabetes 50:1698–1705
Luca, G., C. Nastruzzi, M. Calvitti, E. Becchetti, T. Baroni, L.M. Neri, S. Capitani, G. Basta, P. Brunetti, and R. Calafiore. 2005. Accelerated functional maturation of isolated neonatal porcine cell clusters: in vitro and in vivo results in NOD mice. Cell Transplant 14:249–261
Patience, C., Y. Takeuchi, and R.A. Weiss. 1997. Infection of human cells by an endogenous retrovirus of pigs. Nat Med 3:282–286
Fishman, J.A., and C. Patience. 2004. Xenotransplantation: infectious risk revisited. Am J Transplant 4:1383–1390
Elliott, R.B., L. Escobar, O. Garkavenko, M.C. Croxson, B.A. Schroeder, M. McGregor, G. Ferguson, N. Beckman, and S. Ferguson. 2000. No evidence of infection with porcine endogenous retrovirus in recipients of encapsulated porcine islet xenografts. Cell Transplant 9:895–901
Pakhomov, O., L. Martignat, J. Honiger, B. Clemenceau, P. Sai, and S. Darquy. 2005. AN69 hollow fiber membrane will reduce but not abolish the risk of transmission of porcine endogenous retroviruses. Cell Transplant 14:749–756
Ricci, M., P. Blasi, S. Giovagnoli, C. Rossi, G. Macchiarulo, G. Luca, G. Basta, and R. Calafiore. 2005. Ketoprofen controlled release from composite microcapsules for cell encapsulation: effect on post-transplant acute inflammation. J Control Release 107:395–407
Luca, G., C. Nastruzzi, G. Basta, A. Brozzetti, A. Saturni, D. Mughetti, M. Ricci, C. Rossi, P. Brunetti, and R. Calafiore. 2000. Effects of anti-oxidizing vitamins on in vitro cultured porcine neonatal pancreatic islet cells. Diabetes Nutr Metab 13:301–307
Calafiore, R., G. Basta, G. Luca, A. Lemmi, M.P. Montanucci, G. Calabrese, L. Racanicchi, F. Mancuso, and P. Brunetti. 2006. Microencapsulated pancreatic islet allografts into nonimmunosuppressed patients with type 1 diabetes: first two cases. Diabetes Care 29:137–138
Lum, Z.P., I.T. Tai, M. Krestow, J. Norton, I. Vacek, and A.M. Sun. 1991. Prolonged reversal of diabetic state in NOD mice by xenografts of microencapsulated rat islets. Diabetes 40:1511–1516
Sun, Y., X. Ma, D. Zhou, I. Vacek, and A.M. Sun. 1996. Normalization of diabetes in spontaneously diabetic cynomologus monkeys by xenografts of microencapsulated porcine islets without immunosuppression. J Clin Invest 98:1417–1422
Dufour, J.M., R.V. Rajotte, M. Zimmerman, A. Rezania, T. Kin, D.E. Dixon, and G.S. Korbutt. 2005. Development of an ectopic site for islet transplantation, using biodegradable scaffolds. Tissue Eng 11:1323–1331
Thanos, C.G., R. Calafiore, G. Basta, B.E. Bintz, W.J. Bell, J. Hudak, A. Vasconcellos, P. Schneider, S.J. Skinner, M. Geaney, P. Tan, R.B. Elliot, M. Tatnell, L. Escobar, H. Qian, E. Mathiowitz, and D.F. Emerich. 2007. Formulating the alginate-polyornithine biocapsule for prolonged stability: evaluation of composition and manufacturing technique. J Biomed Mater Res A 83:216–224
Hammerman, M.R. 2004. Organogenesis of endocrine pancreas from transplanted embryonic anlagen. Transpl Immunol 12:249–258
Rogers, S.A., H. Liapis, and M.R. Hammerman. 2003. Intraperitoneal transplantation of pancreatic anlagen. ASAIO J 49:527–532
Rogers, S.A., F. Chen, M.R. Talcott, C. Faulkner, J.M. Thomas, M. Thevis, and M.R. Hammerman. 2007. Long-term engraftment following transplantation of pig pancreatic primordia into non-immunosuppressed diabetic rhesus macaques. Xenotransplantation 14:591–602
Auchincloss, H., and J.V. Bonventre. 2002. Transplanting cloned cells into therapeutic promise. Nat Biotechnol 20:665–666
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Cortesini, R., Calafiore, R. (2009). Pancreas Engineering. In: Meyer, U., Handschel, J., Wiesmann, H., Meyer, T. (eds) Fundamentals of Tissue Engineering and Regenerative Medicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-77755-7_31
Download citation
DOI: https://doi.org/10.1007/978-3-540-77755-7_31
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-77754-0
Online ISBN: 978-3-540-77755-7
eBook Packages: MedicineMedicine (R0)