Abstract
Nonhuman primates (NHP) constitute a highly relevant pre-clinical animal model to develop strategies for beta cell replacement. The close phylogenetic and immunologic relationship between NHP and humans results in cross-reactivity of various biological agents with NHP cells, as well as a very similar cytoarchitecture between islets from human and NHP that is strikingly different from that observed in rodent islets. The composition and location of endocrine cells in human or NHP islets, randomly distributed and associated with blood vessels, have functional consequences and a predisposition for paracrine interactions. Furthermore, translation of approaches that proved successful in rodent models to the clinic has been limited. Consequently, data collected from NHP studies can form the basis for an IND submission to the FDA. This chapter describes in detail the key aspects for isolation of islets from NHP, from organ procurement up to assessment of islet function, comparing and emphasizing the similarities between isolation procedures for human and NHP islets.
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Barton FB, Rickels MR, Alejandro R, Hering BJ, Wease S, Naziruddin B, Oberholzer J, Odorico JS, Garfinkel MR, Levy M, Pattou F, Berney T, Secchi A, Messinger S, Senior PA, Maffi P, Posselt A, Stock PG, Kaufman DB, Luo X, Kandeel F, Cagliero E, Turgeon NA, Witkowski P, Naji A, O’Connell PJ, Greenbaum C, Kudva YC, Brayman KL, Aull MJ, Larsen C, Kay TW, Fernandez LA, Vantyghem MC, Bellin M. Shapiro AM: improvement in outcomes of clinical islet transplantation: 1999–2010. Diabetes Care. 2012;35:1436–45.
Froud T, Ricordi C, Baidal DA, Hafiz MM, Ponte G, Cure P, Pileggi A, Poggioli R, Ichii H, Khan A, Ferreira JV, Pugliese A, Esquenazi VV, Kenyon NS, Alejandro R. Islet transplantation in type 1 diabetes mellitus using cultured islets and steroid-free immunosuppression: Miami experience. Am J Transplant. 2005;5:2037–46.
Harlan DM, Kenyon NS, Korsgren O, Roep BO. Current advances and travails in islet transplantation. Diabetes. 2009;58:2175–84.
Cure P, Pileggi A, Froud T, Messinger S, Faradji RN, Baidal DA, Cardani R, Curry A, Poggioli R, Pugliese A, Betancourt A, Esquenazi V, Ciancio G, Selvaggi G, Burke 3rd GW, Ricordi C, Alejandro R. Improved metabolic control and quality of life in seven patients with type 1 diabetes following islet after kidney transplantation. Transplantation. 2008;85:801–12.
Bassi R, Fiorina P. Impact of islet transplantation on diabetes complications and quality of life. Curr Diab Rep. 2011;11:355–63.
Mineo D, Pileggi A, Alejandro R, Ricordi C. Point: steady progress and current challenges in clinical islet transplantation. Diabetes Care. 2009;32:1563–9.
Mueller KR, Balamurugan AN, Cline GW, Pongratz RL, Hooper RL, Weegman BP, Kitzmann JP, Taylor MJ, Graham ML, Schuurman HJ, Papas KK. Differences in glucose-stimulated insulin secretion in vitro of islets from human, nonhuman primate, and porcine origin. Xenotransplantation. 2013;20:75–81.
Cabrera O, Berman DM, Kenyon NS, Ricordi C, Berggren PO, Caicedo A. The unique cytoarchitecture of human pancreatic islets has implications for islet cell function. Proc Natl Acad Sci U S A. 2006;103:2334–9.
Contreras JL, Eckstein C, Smyth CA, Sellers MT, Vilatoba M, Bilbao G, Rahemtulla FG, Young CJ, Thompson JA, Chaudry IH, Eckhoff DE. Brain death significantly reduces isolated pancreatic islet yields and functionality in vitro and in vivo after transplantation in rats. Diabetes. 2003;52:2935–42.
Rech TH, Crispim D, Rheinheimer J, Barkan SS, Osvaldt AB, Grezzana Filho TJ, Kruel CR, Martini J, Gross JL, Leitao CB. Brain death-induced inflammatory activity in human pancreatic tissue: a case-control study. Transplantation. 2014;97:212–9.
Ricordi C, Lacy PE, Finke EH, Olack BJ, Scharp DW. Automated method for isolation of human pancreatic islets. Diabetes. 1988;37:413–20.
Berman DM, O’Neil JJ, Coffey LC, Chaffanjon PC, Kenyon NM, Ruiz Jr P, Pileggi A, Ricordi C, Kenyon NS. Long-term survival of nonhuman primate islets implanted in an omental pouch on a biodegradable scaffold. Am J Transplant. 2009;9:91–104.
Kenyon NS, Chatzipetrou M, Masetti M, Ranuncoli A, Oliveira M, Wagner JL, Kirk AD, Harlan DM, Burkly LC, Ricordi C. Long-term survival and function of intrahepatic islet allografts in rhesus monkeys treated with humanized anti-CD154. Proc Natl Acad Sci U S A. 1999;96:8132–7.
Kenyon NS, Fernandez LA, Lehmann R, Masetti M, Ranuncoli A, Chatzipetrou M, Iaria G, Han D, Wagner JL, Ruiz P, Berho M, Inverardi L, Alejandro R, Mintz DH, Kirk AD, Harlan DM, Burkly LC, Ricordi C. Long-term survival and function of intrahepatic islet allografts in baboons treated with humanized anti-CD154. Diabetes. 1999;48:1473–81.
Schaefer JH. The normal weight of the pancreas in the adult human being: a biometric study. Anat Rec. 1926;32:119–32.
Caglar V, Kumral B, Uygur R, Alkoc OA, Ozen OA, Demirel H. Study of volume, weight and size of normal pancreas, spleen and kidney in adults autopsies. Forensic Med Anat Res. 2014;2:63–9.
Ichii H, Wang X, Messinger S, Alvarez A, Fraker C, Khan A, Kuroda Y, Inverardi L, Goss JA, Alejandro R, Ricordi C. Improved human islet isolation using nicotinamide. Am J Transplant. 2006;6:2060–8.
Latif ZA, Noel J, Alejandro R. A simple method of staining fresh and cultured islets. Transplantation. 1988;45:827–30.
Kenmochi T, Miyamoto M, Mullen Y. Protection of mouse islet isografts from nonspecific inflammatory damage by recipient treatment with nicotinamide and 15-deoxyspergualin. Cell Transplant. 1996;5:41–7.
Ichii H, Pileggi A, Molano RD, Baidal DA, Khan A, Kuroda Y, Inverardi L, Goss JA, Alejandro R, Ricordi C. Rescue purification maximizes the use of human islet preparations for transplantation. Am J Transplant. 2005;5:21–30.
London NJM, Robertson GSM, Chadwick DR, James RFL, Bell PRF. Adult islet purification. Austin: R.G. Lanades Company; 1995.
Ricordi C, Gray DW, Hering BJ, Kaufman DB, Warnock GL, Kneteman NM, Lake SP, London NJ, Socci C, Alejandro R, et al. Islet isolation assessment in man and large animals. Acta Diabetol Lat. 1990;27:185–95.
Kissler HJ, Niland JC, Olack B, Ricordi C, Hering BJ, Naji A, Kandeel F, Oberholzer J, Fernandez L, Contreras J, Stiller T, Sowinski J, Kaufman DB. Validation of methodologies for quantifying isolated human islets: an islet cell resources study. Clin Transplant. 2010;24:236–42.
Buchwald P, Berman DM, Khan A, Szust J, Rabassa A, Fraker C, Echeverri F, Bernal A, Inverardi L, Kenyon NS, Ricordi C. Assessment of the accuracy and reproducibility of a digital image analysis-based automatic islet cell counter (ICC) using microsphere mixtures as well as human and NHP islets. In: Cell Transplant Society – International Xenotransplantation Association (CTS-IXA) 2011 Joint Congress. Miami, Cell Medicine, p. P111.
Idahl LA. A micro perifusion device for pancreatic islets allowing concomitant recordings of intermediate metabolites and insulin release. Anal Biochem. 1972;50:386–98.
Ranuncoli A, Cautero N, Ricordi C, Masetti M, Molano RD, Inverardi L, Alejandro R, Kenyon NS. Islet cell transplantation: in vivo and in vitro functional assessment of nonhuman primate pancreatic islets. Cell Transplant. 2000;9:409–14.
Balamurugan AN, Naziruddin B, Lockridge A, Tiwari M, Loganathan G, Takita M, Matsumoto S, Papas K, Trieger M, Rainis H, Kin T, Kay TW, Wease S, Messinger S, Ricordi C, Alejandro R, Markmann J, Kerr-Conti J, Rickels MR, Liu C, Zhang X, Witkowski P, Posselt A, Maffi P, Secchi A, Berney T, O’Connell PJ, Hering BJ, Barton FB. Islet product characteristics and factors related to successful human islet transplantation from the Collaborative Islet Transplant Registry (CITR) 1999–2010. Am J Transplant. 2014;14:2595–606.
Berman DM, Cabrera O, Kenyon NM, Miller J, Tam SH, Khandekar VS, Picha KM, Soderman AR, Jordan RE, Bugelski PJ, Horninger D, Lark M, Davis JE, Alejandro R, Berggren PO, Zimmerman M, O’Neil JJ, Ricordi C, Kenyon NS. Interference with tissue factor prolongs intrahepatic islet allograft survival in a nonhuman primate marginal mass model. Transplantation. 2007;84:308–15.
Ricordi C, Scharp DW, Lacy PE. Reversal of diabetes in nude mice after transplantation of fresh and 7-day-cultured (24 degrees C) human pancreatic islets. Transplantation. 1988;45:994–6.
Ricordi C, Zeng YJ, Alejandro R, Tzakis A, Venkataramanan R, Fung J, Bereiter D, Mintz DH, Starzl TE. In vivo effect of FK506 on human pancreatic islets. Transplantation. 1991;52:519–22.
Acknowledgement
I want to thank Dr. Norma S. Kenyon, whose expert guidance and support enabled me to become proficient in the field of NHP islet isolation .
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Berman, D.M. (2016). Isolation of Pancreatic Islets from Nonhuman Primates. In: Ramírez-Domínguez, M. (eds) Pancreatic Islet Isolation. Advances in Experimental Medicine and Biology, vol 938. Springer, Cham. https://doi.org/10.1007/978-3-319-39824-2_5
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DOI: https://doi.org/10.1007/978-3-319-39824-2_5
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