The Effects of Using Pancreases Obtained from Brain-Dead Donors for Clinical Islet Transplantation in Japan

Ito, Taihei; Kenmochi, Takashi; Kurihara, Kei; Kawai, Maki; Aida, Naohiro; Akashi, Yumi; Kato, Sakurako

doi:10.3390/jcm8091430

Cited by 6 publications

(8 citation statements)

References 15 publications

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“…Proof of principle to use organs from donors after circulatory death as additional source for islet cell transplantation was already shown previously. While some reports included donors where circulatory arrest occurs under uncontrolled circumstances (DCD category II) and that are subject to long and not well documented periods of warm ischemia [28][29][30], the remaining cohorts involved highly selected DCD III [10,11,16,17].…”

Section: Discussionmentioning

confidence: 99%

Lower beta cell yield from donor pancreases after controlled circulatory death prevented by shortening acirculatory warm ischemia time and by using IGL-1 cold preservation solution

et al. 2021

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Organs from donors after controlled circulatory death (DCD III) exhibit a higher risk for graft dysfunction due to an initial period of warm ischemia. This procurement condition can also affect the yield of beta cells in islet isolates from donor pancreases, and hence their use for transplantation. The present study uses data collected and generated by our Beta Cell Bank to compare the number of beta cells in isolates from DCD III (n = 141) with that from donors after brain death (DBD, n = 609), before and after culture, and examines the influence of donor and procurement variables. Beta cell number per DCD III-organ was significantly lower (58 x 106 versus 84 x 106 beta cells per DBD-organ; p < 0.001) but their purity (24% insulin positive cells) and insulin content (17 μg / 106 beta cells in DCD III-organs versus 19 μg / 106 beta cells in DBD-organs) were similar. Beta cell number correlated negatively with duration of acirculatory warm ischemia time above 10 min; for shorter acirculatory warm ischemia time, DCD III-organs did not exhibit a lower beta cell yield (74 x 106 beta cells). Use of Institut Georges Lopez-1 cold preservation solution instead of University of Wisconsin solution or histidine-tryptophan-ketoglutarate also protected against the loss in beta cell yield from DCD III-organs (86 x 106 for IGL-1 versus 54 x 106 and 65 x 106 beta cells respectively, p = 0.042). Multivariate analysis indicates that both limitation of acirculatory warm ischemia time and use of IGL-1 prevent the reduced beta cell yield in islet cell isolates from DCD III-organs.

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Section: Discussionmentioning

confidence: 99%

Lower beta cell yield from donor pancreases after controlled circulatory death prevented by shortening acirculatory warm ischemia time and by using IGL-1 cold preservation solution

et al. 2021

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“…One of our suggestions for older patients with a long history of diabetes on the waiting list for pancreas transplantation is islet transplantation. The increased number of BDDs following the revision resulted in a decreased rate of pancreas utilization for organ transplantation, and consequent improvements in islet isolation by increased donation from BDDs have improved the chances for performing islet transplantation in patients with type 1 diabetes 25 . In addition, islet transplantation has been covered by Japanese national health insurance since 2020.…”

Section: Discussionmentioning

confidence: 99%

Impact of the revision of the law on pancreatic transplants in Japan—An analysis of the Japanese Pancreas Transplants Registry

Ito

Kenmochi

Aida

et al. 2021

J Hepato Biliary Pancreat

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Background In Japan, it has been about 10 years since the revision of the law on donating brain‐dead organs. The present study compared the outcomes of pancreatic transplant before and after the revision of the law. Methods The 437 patients who had received pancreas transplantation were divided into two groups according to the time when pancreas transplantation was performed between era 1 (before the revision) and 2 (after the revision), and compared in the patient and pancreas graft survival. Results While the annual number of brain‐dead donors was <10 in era 1, and this number significantly increased in era 2 to >50. This resulted in an increased number of pancreas transplantations: >30 cases per year. The comparison data after a propensity score‐matched analysis revealed that the death‐censored pancreatic graft survival at 1, 3, and 5 years after pancreas transplantation in era 2 was 94.9%, 92.0%, and 92.0%, which, while lacking significance, tended to be better than the values of 90.5%, 83.1%, and 78.2%, respectively, in era 1. Conclusions The revision of the law on donating brain‐dead organs increased the number of pancreas transplantations. Technical improvements in surgery due to increased experience with performing pancreas transplants may help improve pancreatic graft survival.

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“…There are perceived added risks for the utilization of DCD organs as DCD kidneys and livers have been shown to be more susceptible to the harmful effects of warm and cold ischemia [ 6 , 7 , 8 , 9 ]. Islet isolation from DCD donors has shown to result in lower yields compared with DBD pancreases (87 000–100 000 IEQ less) [ 10 , 11 ]. Therefore, donor characteristics are often more favorable for DCD pancreases: younger age, more often male donors, without a recent history of cardiac arrest, leading to comparable viability, and function after islet isolation [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Hypothermic oxygenated machine perfusion of the human pancreas for clinical islet isolation: a prospective feasibility study

et al. 2021

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Summary Due to an increasing scarcity of pancreases with optimal donor characteristics, islet isolation centers utilize pancreases from extended criteria donors, such as from donation after circulatory death (DCD) donors, which are particularly susceptible to prolonged cold ischemia time (CIT). We hypothesized that hypothermic machine perfusion (HMP) can safely increase CIT. Five human DCD pancreases were subjected to 6 h of oxygenated HMP. Perfusion parameters, apoptosis, and edema were measured prior to islet isolation. Five human DBD pancreases were evaluated after static cold storage (SCS). Islet viability, and in vitro and in vivo functionality in diabetic mice were analyzed. Islets were isolated from HMP pancreases after 13.4 h [12.9–14.5] CIT and after 9.2 h [6.5–12.5] CIT from SCS pancreases. Histological analysis of the pancreatic tissue showed that HMP did not induce edema nor apoptosis. Islets maintained >90% viable during culture, and an appropriate in vitro and in vivo function in mice was demonstrated after HMP. The current study design does not permit to demonstrate that oxygenated HMP allows for cold ischemia extension; however, the successful isolation of functional islets from discarded human DCD pancreases after performing 6 h of oxygenated HMP indicates that oxygenated HMP may be a useful technology for better preservation of pancreases.

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The Effects of Using Pancreases Obtained from Brain-Dead Donors for Clinical Islet Transplantation in Japan

Cited by 6 publications

References 15 publications

Lower beta cell yield from donor pancreases after controlled circulatory death prevented by shortening acirculatory warm ischemia time and by using IGL-1 cold preservation solution

Lower beta cell yield from donor pancreases after controlled circulatory death prevented by shortening acirculatory warm ischemia time and by using IGL-1 cold preservation solution

Impact of the revision of the law on pancreatic transplants in Japan—An analysis of the Japanese Pancreas Transplants Registry

Hypothermic oxygenated machine perfusion of the human pancreas for clinical islet isolation: a prospective feasibility study

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