ISLETS

T. Saito¹, M. Gotoh², S. Uemoto³, T. Kenmochi⁴, Y. Kuroda⁵, Y. Yasunami⁶, S. Satomi⁷, T. Itoh⁸, T. Kitamoto⁹, S. Mohri¹⁰, S. Teraoka^11
1Surgery, Fukushima Medical University, Fukushima/JAPAN, ², Fukushima Medical University, Fukushima/JAPAN, ³Hepatopancreatobillary Surgery And Liver Transplantation, Kyoto University Hospital, Kyoto/JAPAN, ⁴Department Of Surgery, Chiba-East National Hospital, Chiba/JAPAN, ⁵Surgery, Kobe University, Kobe/JAPAN, ⁶Department Of Regenerative Medicine And Transplantation, Fukuoka University, Fukuoka/JAPAN, ⁷Transplantation, Reconstruction And Endoscopic Surgery, Tohoku University, Sendai/JAPAN, ⁸Surgery, Osaka University, Osaka/JAPAN, ⁹Department Of Prion Research, Tohoku University, Sendai/JAPAN, ¹⁰Prion Disease Research, National Institute of Animal Health, Tsukuba/JAPAN, ¹¹Kidney Center, Department Of Surgery, Tokyo Women's Medical University, Tokyo/JAPAN

Body: Introduction: A potential risk of introduction of transmissible spongiform encephalopathy (TSE) into islet cells was pointed out by recognizing that Liberase HI is isolated from Clostridium histolyticum grown in media that contains brain-heart infusion broth. In Japan, islet transplantation program had been performed using the Liberase HI as a national team in the Japanese Society for Pancreas and Islet Transplantation. We have performed 65 isolations from non-heart beating donors and 34 transplants in 18 patients. One living related and one auto-transplantation were also carried out. Here, we summarize actions of our Society in order to obtain long-term careful follow up of these recipients. On the March 27th 2007, we obtained this risk information from several members of our Society. Collecting the facts, we decided to stop the islet transplantation program using the Liberase, because of the potential risk of Creutzfeldt-Jakob disease (CJD) by transmission of TSE into recipients, although the prevalence of BSE in US cattle is extremely low. We informed the previous recipients of this risk information and providing consultation service in each transplant institute. Then we sat up an ad hoc committee to deal with long-term care of these recipients. The committee took concrete steps for the two major concerns: a risk of TSE in the collagenase and follow up of recipients. Methods: All the recipients after taking diffusion MRI and EEG were scheduled to be evaluated and followed by CJD specialists. Bioassay of BSE prion in the collagenase used was planned using knock-in mice expressed bovine prion protein, which could offer the most sensitive assay currently available and detect contaminated prion until 1x10(4) dilution. Inactivated Liberase HI, by heating at 100℃ for 10 minutes, injected into the abdominal cavity of the knock-in mice. Four months after injection, prion infectivity in Liberase HI was evaluated by immunohistochemical staining and Western blotting assay of spleen using anti- PrP antibodies. Polyclonal antibody (pAb) B103 (Horiuchi et al., 1995) and monoclonal antibodies (mAbs) 44B1 (Kim et al., 2004), T2 (Hayashi et al., 2005) and 3F4 (Signet Laboratories) were used as primary antibodies. Results: Western blotting and immunohistochemical staining revealed that the prion contained in Liberase HI below the minimum detectable sensitivity of these assays. No recipients showed CJD infection by evaluation of CJD specialists using diffusion MRI and EEG. Conclusion: In conclusion, recipients of islet transplantation in Japan revealed no infection findings of CJD for 3 years of follow up, and the bioassay of prion showed no infectivity of Liberase HI used for our recipients.

Disclosure: All authors have declared no conflicts of interest.