The use of non-heart-beating donors for isolated pancreatic islet transplantation

Abstract

Recent improvements in isolated islet transplantation indicate that this therapy may ultimately prove applicable to patients with type I diabetes. An obstacle preventing widespread application of islet transplantation is an insufficient supply of cadaveric pancreata. Non-heart-beating donors (NHBDs) are generally not deemed suitable for whole-organ pancreas donation and could provide a significant source of pancreata for islet transplantation. Isolated pancreatic islets prepared from 10 NHBDs were compared with those procured from 10 brain-dead donors (BDDs). The success of the isolation for the two groups was analyzed for preparation purity, quality, and recovered islet mass. The function of NHBD and BDD islets was evaluated using in vitro and in vivo assays. On the basis of the results of this analysis, an NHBD isolated islet allograft was performed in a type I diabetic. The recovery of islets from NHBDs was comparable to that of control BDDs. In vitro assessment of NHBD islet function revealed function-equivalent BDD islets, and NHBD islets transplanted to non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice efficiently reversed diabetes. Transplantation of 446,320 islet equivalents (IEq) (8,500 IEq/kg of recipient body weight) from a single NHBD successfully reversed the diabetes of a type I diabetic recipient. Normally functioning pancreatic islets can be isolated successfully from NHBDs. A single donor transplant from an NHBD resulted in a state of stable insulin independence in a type I diabetic recipient. These results indicate that NHBDs may provide an as yet untapped source of pancreatic tissue for preparation of isolated islets for clinical transplantation.

Structural and Functional Abnormalities in the Islets Isolated From Type 2 Diabetic Subjects

“…Refinements of techniques in organ preservation and islet isolation have allowed isolation of highquality islets from pancreata subjected to prolonged cold ischemia and from pancreata of older donors (35)(36)(37). We have also recently demonstrated the feasibility of using pancreata from non-heart-beating donors for successful islet transplantation (38). All these efforts are aimed at salvaging islets, even those from "marginal donors" that might previously have been discarded.…”

THERAPY OF ENDOCRINE DISEASE: Islet transplantation for type 1 diabetes: so close and yet so far away

“…Due to the potential ischemic damage to exocrine cells which may induce pancreatitis, NHBDs' pancreata are not preferred for whole pancreas transplantation. A study by Markmann et al (16) has reported that the quality of ten NHBDs' pancreatic islets was proven to be similar to islets obtained from ten BDDs.…”

Regenerative Medicine and Tissue Engineering for the Treatment of Diabetes

“…Using the Edmonton protocol, type 1 diabetic patients who had severe hypoglycemic episodes became insulin independent and free from hypoglycemic episodes after allogenic islet transplantation (Shapiro et al, 2000). The allogeneic islet transplantation has been expanded using non-heart beating donors (Markmann et al, 2003;Matsumoto et al, 2006b) and even living donor (Matsumoto et al, 2005(Matsumoto et al, , 2006a. However, the drawbacks of the Edmonton protocol include necessity of multiple donor organs, unstable islet isolation results, necessity of immunosuppressive drugs, difficulty of maintaining long-term insulin independence and severe shortage of donor organs (Ryan et al, 2005;Shapiro et al, 2006).…”