Current status of pancreatic islet transplantation

Abstract

DM (diabetes mellitus) is a metabolic disorder of either absolute or relative insulin deficiency. Optimized insulin injections remain the mainstay life-sustaining therapy for patients with T1DM (Type I DM) in 2006; however, a small subset of patients with T1DM (approx. 10%) are exquisitely sensitive to insulin and lack counter-regulatory measures, putting them at higher risk of neuroglycopenia. One alternative strategy to injected insulin therapy is pancreatic islet transplantation. Islet transplantation came of age when Paul E. Lacy successfully reversed chemical diabetes in rodent models in 1972. In a landmark study published in 2000, Shapiro et al. [A. M. Shapiro, J. R. Lakey, E. A. Ryan, G. S. Korbutt, E. Toth, G. L. Warnock, N. M. Kneteman and R. V. Rajotte (2000) N. Engl. J. Med. 343, 230-238] reported seven consecutive patients treated with islet transplants under the Edmonton protocol, all of whom maintained insulin independence out to 1 year. Substantial progress has occurred in aspects of pancreas procurement, transportation (using the oxygenated two-layer method) and in islet isolation (with controlled enzymatic perfusion and subsequent digestion in the Ricordi chamber). Clinical protocols to optimize islet survival and function post-transplantation improved dramatically with the introduction of the Edmonton protocol, but it is clear that this approach still has potential limitations. Newer pharmacotherapies and interventions designed to promote islet survival, prevent apoptosis, to promote islet growth and to protect islets in the long run from immunological injury are rapidly approaching clinical trials, and it seems likely that clinical outcomes of islet transplantation will continue to improve at the current exponential pace.

The effects of oral carvacrol treatment against H2O2induced injury on isolated pancreas islet cells of rats

“…1,15 However, the procedures during the isolation process may cause cellular dysfunction. It has been previously reported that oxidative stress plays a major role in triggering the death of islets.…”

Revisão sistemática sobre alotransplantes de ilhotas de Langerhans em roedores: análise de sítio de transplante e tempo de sobrevida

“…Os primeiros sucessos em aloenxertos de ilhotas no tratamento cirúrgico de diabetes ocorreram em 1990 com Scharp et al 4 que alcançaram a insulino-independência em um paciente portador de DM1 em um intervalo de um mês. No entanto, muitas dificuldades técnicas foram encontradas para prosseguir no desenvolvimento da reprodução deste experimento.…”

“…Na década de 1991 a 2000, foram realizadas 450 tentativas de transplante de ilhotas em pacientes com DM1, com índice de sucesso de apenas 8%. 50% do sucesso dos casos foram obtidos e reportados, quando os pacientes tinham se tornado diabéticos por terem sido submetidos à pancreatectomia 4 . Até que em 1999/2000, Shapiro et al obtiveram sucesso na independência de insulina em 7 pacientes diabéticos, realizando os experimentos com base no protocolo modificado de Edmonton 7 .…”

Untitled

“…Effective treatment demands transplant of 8000 to 10 000 islet equivalents per kilogram of patient body weight. 1 The main problem related to islet transplant is shortage of human pancreata. Solutions for deficiency of organs from deceased donors may be cryopreservation of isolated islets, which involves tissue collection and long-term storage.…”