Reduction of early graft loss after intraportal porcine islet transplantation in monkeys

作者: Pleunie P. M. Rood , Rita Bottino , A N. Balamurugan , Cindy Smetanka , David Ayares

DOI: 10.1097/01.TP.0000250680.36942.C6

关键词:

摘要: Background Pig islets constitute a possible resolution to the shortage of human for transplantation. After intraportal infusion porcine in primates, many are lost through what has been termed instant blood-mediated inflammatory reaction (IBMIR). We report on our experience with IBMIR. Methods Ten monkeys underwent islet Immunosuppressive therapy was conventional agents (n=3) or based costimulation blockade (n=7). Treatment specific IBMIR administered eight monkeys; two additional received no such (group 1). Cobra venom factor completely inhibited complement activity four 2) and dextran sulfate provided anticoagulation 3). Islet graft function monitored by following blood glucose, insulin requirement, C-peptide values. Results In that neither cobra nor 1), there rapid destruction indicated severe hypoglycemia need dextrose infusion; levels were initially low further reduction occurred within first five days. both groups 2 3, significantly less some reversal diabetes. However, when 40,000 IEQ/kg infused, normoglycemia days, but 80,000 infused one case, more persistent. observed even normal range healthy nondiabetic pigs, these not sufficient maintain monkeys. Conclusions Although pretransplantation depletion reduces xenograft loss significantly, alone is prevent

参考文章(31)
Christian Toso, Daniel Brandhorst, José Oberholzer, Frédéric Triponez, Léo Bühler, Philippe Morel, Isolation of adult porcine islets of Langerhans. Cell Transplantation. ,vol. 9, pp. 297- 305 ,(2000) , 10.1177/096368970000900301
Alfredo Lorenzo, Bronwyn Razzaboni, Gordon C. Weir, Bruce A. Yankner, Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitus Nature. ,vol. 368, pp. 756- 760 ,(1994) , 10.1038/368756A0
C. Knosalla, D.J.J. Ryan, K. Moran, B. Gollackner, W. Schuler, D.H. Sachs, M. Awwad, H.-J. Schuurman, D.K.C. Cooper, Initial experience with the human anti-human CD154 monoclonal antibody, ABI793, in pig-to-baboon xenotransplantation. Xenotransplantation. ,vol. 11, pp. 353- 360 ,(2004) , 10.1111/J.1399-3089.2004.00148.X
Dilip S. Nath, Bernhard J. Hering, Islet cells replacement therapy. Clinics in Laboratory Medicine. ,vol. 25, pp. 541- 556 ,(2005) , 10.1016/J.CLL.2005.06.005
A. N. Balamurugan, Y. Chang, S. Bertera, A. Sands, V. Shankar, M. Trucco, R. Bottino, Suitability of human juvenile pancreatic islets for clinical use Diabetologia. ,vol. 49, pp. 1845- 1854 ,(2006) , 10.1007/S00125-006-0318-0
A. N. Balamurugan, Yigang Chang, John J. Fung, Massimo Trucco, Rita Bottino, Flexible management of enzymatic digestion improves human islet isolation outcome from sub-optimal donor pancreata. American Journal of Transplantation. ,vol. 3, pp. 1135- 1142 ,(2003) , 10.1046/J.1600-6143.2003.00184.X
Yukihide Yonekawa, Shinichi Matsumoto, Teru Okitsu, Takashi Arata, Yasuhiro Iwanaga, Hirofumi Noguchi, Hideo Nagata, John J. O'neil, Koichi Tanaka, Effective islet isolation method with extremely high islet yields from adult pigs. Cell Transplantation. ,vol. 14, pp. 757- 762 ,(2005) , 10.3727/000000005783982512
Olle Korsgren, B Nilsson, C Berne, M Felldin, A Foss, R Kallen, T Lundgren, K Salmela, A Tibell, G Tufveson, Current status of clinical islet transplantation. Transplantation. ,vol. 79, pp. 1289- 1293 ,(2005) , 10.1097/01.TP.0000157273.60147.7C
Bernhard J Hering, Martin Wijkstrom, Melanie L Graham, Maria Hårdstedt, Tor C Aasheim, Tun Jie, Jeffrey D Ansite, Masahiko Nakano, Jane Cheng, Wei Li, Kathleen Moran, Uwe Christians, Colleen Finnegan, Charles D Mills, David E Sutherland, Pratima Bansal-Pakala, Michael P Murtaugh, Nicole Kirchhof, Henk-Jan Schuurman, Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates. Nature Medicine. ,vol. 12, pp. 301- 303 ,(2006) , 10.1038/NM1369