Islet transplantation

Another biomedical appHcation of mictocapsules is the encapsulation of Hve mammalian ceUs for transplantation into humans. The purpose of encapsulation is to protect the transplanted ceUs or organisms from rejection by the host. The capsule sheU must prevent entrance of harmful agents into the capsule, aUow free transport of nutrients necessary for ceU functioning into the capsule, and aUow desirable ceUular products to freely escape from the capsule. This type of encapsulation has been carried out with a number of different types of Hve ceUs, but studies with encapsulated pancreatic islets or islets of Langerhans ate most common. The alginate—poly(L-lysine) encapsulation process originally developed in 1981 (54) catalyzed much of the ceU encapsulation work carried out since. A discussion of the obstacles to the appHcation of microencapsulation in islet transplantation reviewed much of the mote recent work done in this area (55). Animal ceU encapsulation has also been researched (56). 

Teramura Y, Iwata H (2011) Improvement of graft survival by surface modification with poly (ethylene glycol)-lipid and urokinase in intraportal islet transplantation. Transplantation 91 271-278... 

Bennet W, Sundberg B, Cg G et al (1999) Incompatibility between human blood and isolated islets of Langerhans a finding with implications for clinical intraportal islet transplantation Diabetes 48 1907-1914... 

Moberg L, Johansson H, Lukinius A et al (2002) Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation. Lancet 360 2039-2045... 

Goosen MFA (1994) In Lanza RP, Chick WM (eds) Pancreatic islet transplantation, vol III immunoisolation of pancreatic islets. RG Landes, Austin, TX... 

Hakin, N. 2002. Pancreas and Islet Transplantation. Oxford University Press. 

Secchi, A., Di Carlo, V., and Pozza, G. 1997. Pancreas and islet transplantation - current progress, problems and perspectives. Hormone and Metabolic Research 29(1), 1-8. 

Robertson RP. Medical progress islet transplantation as a treatment for diabetes - a work in progress. N Engl J Med 2004 350 694-705. 

Soon-Shiong P, Heintz RE, Merideth N, Yao QX, Yao ZW, Zheng TL, Murphy M, Moloney MK, Schmehl M, Harris M, Mendez R, Mendez R, Sandford PA. Insulin independence in a type-1 diabetic patient after encapsulated islet transplantation. Lancet 1994 343 950-951. 

Shapiro AMJ, Lakey JRT, Ryan EA. 2000. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. NEJM. 343 230-238. 

Genetic modification of the islet transplant in vitro prior to transplantation could improve its survival, function, and safety following transplantation The shortage of transplantable P cells can be overcome by the generation of j3-cell lines. In addition to providing an abundant source of P cells, cell lines represent a... 

Shapiro AM, Lakey JR, Paty BW, et al. Strategic opportunities in clinical islet transplantation. Transplantation. 2005 79 1304-1307. 

Examples of candidate transgenes with potential utility in the prevention of islet transplant rejection... 

Potential utility of rAAV-mediatedgene therapy for islet transplantation and prevention of autoimmunity recurrence in type 1 diabetes... 

Fujita, J., Zhou, J.-P., Szot, G., Ostrega, D., Baldwin, A., Park, C.-G., Thompson, C., Bluestone, J. and Polonsky, K. (2000). Bcl-xL overexpression prevents cytokine-induced dysfunction and apoptosis in pancreatic b cells and prolongs graft survival in islet transplantation. Diabetes 49 (Abstract). 

Hering, B. J., Browatzki, C. C., Schultz, A., Bretzel, R. G. and Federlin, K. F. (1993). Clinical islet transplantation—registry report, accomplishments in the past and future research needs. Cell Transplant. 2, 269-282. 

Masetti, M., Inverardi, L., Ranuncoli, A., Iaria, G., Lupo, F., Vizzardelli, C., Kenyon, N. S., Alejandro, R. and Ricordi, C. (1997). Current indications and limits of pancreatic islet transplantation in diabetic nephropathy. J. Nephrol. 10, 245-252. 

Rabinovitch, A., Suarez-Pinzon, W. L., Sorensen, O., Bleackley, R. C., Power, R. F. and Rajotte, R. V. (1995). Combined therapy with interleukin-4 and interleukin-10 inhibits autoimmune diabetes recurrence in syngeneic islet-transplanted nonobese diabetic mice. Analysis of cytokine mRNA expression in the graft.Transplantation 60, 368-374. 

Shapiro, A. M., Lakey, J. R., Ryan, E. A., Korbutt, G. S., Toth, E., Warnock, G. L, Kneteman, N. M. and Rajotte, R. V. (2000). Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N. Engl. J. Med. 343, 230-238. 

Stevens, R. B., Lokeh, A., Ansite, J. D., Field, M. J., Gores, P. F. and Sutherland, D. E. (1994). Role of nitric oxide in the pathogenesis of early pancreatic islet dysfunction during rat and human intraportal islet transplantation. Transplant. Proc. 26, 692. 

Eliaschewitz FG, Aita CA, Genzini T, Noronha IL, Lojudice FH, Labriola L, Krogh K, Oliveira EM, Silva IC, Mendonca Z, Franco D, Miranda MP, Noda E, de Castro LA, Andreolli M, Goldberg AC, Sogayar MC (2004), First Brazilian pancreatic islet transplantation in a patient with type 1 diabetes mellitus, Transplant. Proc. 36 1117-1118. 

Transplantation of islets of Langerhans as a means of treating insulin-dependent diabetes mellitus has become an important field of interest [217-219]. However, tissue rejection and relapse of the initial autoimmune process have limited the success of this treatment. Immunoisolation of islets in semipermeable microcapsules has been proposed to prevent their immune destruction [220, 221]. Nevertheless, a pericapsular cellular reaction eventually develops around micro-encapsulated islets, inducing graft failure [222]. Since empty microcapsules elicit a similar reaction [223], the reaction is not related to the presence of islets within the capsule but is, at least partially, caused by the capsule itself. Consequently, microcapsule biocompatibility appears to constitute a major impediment to the successful microencapsulated islet transplantation. 

Juang, J-H. Bonner-Weir, S. Vacanti, J.P. Weir, G.C. Outcome of subcutaneous islet transplantation improved by a polymer device. Transplantation Proceedings 1995, 27 (6), 3215-3217. 

Senior PA, Paty BW, Cockfield SM, Ryan EA, Shapiro AM. Proteinuria developing after clinical islet transplantation resolves with sirolimus withdrawal and increased tacrolimus dosing. Am J Transplant 2005 5 2318-2323. 

In Type-I diabetes, which is due to the loss of insulin-producing cells as a consequence of autoimmune disorders, substitution of insulin is the most important measure. However, merely to inject one daily dose is not an adequate therapy. Here, the objective is to mimic the daily variations in plasma insulin which are closely related to food intake. One such attempt which has improved microvascular complications is intensified insulino-therapy through multiple daily injections of insulin. Another approach is to develop techniques of islet transplantation and using a bioartificial pancreas. In the case of islet transplantation, tissues will not only respond to changes in blood glucose levels but also to hormones of the entero-insular axis. 

Robertson RP, Davis C, Larsen J, et al. Pancreas and islet transplantation for patients with diabetes mellitus (technical review). Diabetes Care 2000 23 112-116. 

Pancreas transplantation, with immunosuppression therapy, has become clinically acceptable (10) at least for those who also receive kidney transplants (despite the nephrotoxicity of cyclosporin). Islet transplants are simpler sur-... 

Immunoisolation may also have an advantage in preventing the autoimmune destruction of the transplanted islets (27) by separating them from the host (T-cells or autoantibodies) by the permselective membrane. Although the detailed mechanism of islet cell damage is unknown, evidence from spontaneously diabetic BB rats indicates that the rapid failure of islet transplants, even in twins (28), may be due to a recurrence of autoimmune disease rather than the conventional transplant rejection phenomenon (29). 

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