{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:42:54Z","timestamp":1792276974014,"version":"4.4.0"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,9,28]],"date-time":"2009-09-28T00:00:00Z","timestamp":1254096000000},"content-version":"vor","delay-in-days":89,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2009,7]]},"abstract":"<jats:sec><jats:label\/><jats:p><jats:bold>Abstract:\u2002<\/jats:bold> Pre\u2010clinical efficacy and complication data required to justify a porcine islet transplantation clinical trial have been considered. To be relevant to clinical islet transplantation, pre\u2010clinical data should be obtained in a pig\u2010to\u2010diabetic non\u2010human primate (NHP) model. In view of the difficulties of maintaining immunosuppressed NHPs for long periods of time, flexibility must be allowed with regard to the following recommendations. A pre\u2010clinical trial would be deemed a success if five of eight consecutive experiments in NHPs with proven diabetes meet the following guidelines.<\/jats:p><jats:p>1. The fasting and non\u2010fasting blood glucose levels have been maintained in the NHP at approximately &lt;150\u2003mg\/dl (&gt;8.3\u2003mmol\/l) and &lt;200\u2003mg\/dl (11.1\u2003mmol\/l), respectively, throughout a 6\u2010month follow\u2010up period (preferably with observations in one or two NHPs extending to 12\u2003months).<\/jats:p><jats:p>2. After the transplantation of adult or fetal\/neonatal pig islets, no or greatly reduced exogenous insulin has been required after the development of a state of normoglycemia (that may take approximately the first 4\u2003weeks for adult and 12\u2003weeks for fetal\/neonatal islets, respectively), except under exceptional, temporary circumstances.<\/jats:p><jats:p>3. Sequential intravenous glucose tolerance tests [at 1, 3, 6 (and 12) months post\u2010transplantation] or arginine stimulation tests have indicated a significant response to glucose in the form of porcine C\u2010peptide in the absence of a significant response of NHP C\u2010peptide.<\/jats:p><jats:p>4. Histologic study of the native pancreas (if present) after necropsy indicates no or minimal insulin\u2010positive \u03b2 cells, and histologic examination of the liver or other site of islet transplantation indicates multiple viable insulin\u2010positive cells.<\/jats:p><jats:p>5. Numerous or serious life\u2010threatening complications have not been associated with the transplantation procedure, immunosuppressive regimen, tolerance\u2010inducing regimen, or encapsulation of the islets.<\/jats:p><jats:p>Pre\u2010clinical trials in which the recipient NHPs do not require continuing immunosuppressive therapy (e.g., when encapsulated islets have been transplanted) may possibly be considered acceptable as a basis for a clinical trial with slightly less stringent requirements with regard to points (1) and (2), but would be expected to provide evidence that points (3), (4), and (5) had been achieved.<\/jats:p><\/jats:sec><jats:sec><jats:title>Table of Contents<\/jats:title><jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Introduction<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Induction of diabetes in the non\u2010human primate potential recipient<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Porcine islet transplantation<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Immunotherapeutic protocol<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Determination of success of islet transplantation<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Conclusions<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1399-3089.2009.00543.x","type":"journal-article","created":{"date-parts":[[2009,9,28]],"date-time":"2009-09-28T06:59:04Z","timestamp":1254121144000},"page":"229-238","source":"Crossref","is-referenced-by-count":54,"title":["Chapter 4: Pre\u2010clinical efficacy and complication data required to justify a clinical trial"],"prefix":"10.1111","volume":"16","author":[{"given":"David K. C.","family":"Cooper","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Casu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,9,28]]},"reference":[{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2006.01336.x"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.3727\/000000006783982052"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1369"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3089.2005.00206.x"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000250680.36942.c6"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3181840f55"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-007-0844-4"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-67-4-785"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.40.6.673"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.2337\/db07-0790"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/mpa.0b013e3181452886"},{"key":"e_1_2_10_13_2","article-title":"Dosing streptozotocin based on body surface area is superior to dosing based on body weight","author":"Wijkstrom M","year":"2003","journal-title":"Int Cong Cell Transpl Soc"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.mpa.0000235307.04110.a2"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/59.11.1081"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3089.2009.00541.x"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000208610.75997.20"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3089.2002.1o044.x"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000146504.73727.13"},{"key":"e_1_2_10_20_2","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1210\/jcem-65-1-30","article-title":"Effects of age, duration and treatment of insulin\u2010dependent diabetes mellitus on residual beta\u2010cell function: observations during eligibility testing for the Diabetes Control and Complications Trial (DCCT)","volume":"65","author":"The DCCT Research Group","year":"1987","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.1.250"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.2337\/db07-0742"},{"key":"e_1_2_10_23_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.1.100"},{"key":"e_1_2_10_24_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111542"},{"key":"e_1_2_10_25_2","first-page":"920","volume-title":"Lange Endocrinology \u2013 Basic and Clinical Endocrinology","author":"Greenspan FS","year":"2006"},{"key":"e_1_2_10_26_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.11.3160"}],"container-title":["Xenotransplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1399-3089.2009.00543.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1399-3089.2009.00543.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T01:52:52Z","timestamp":1697507572000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1399-3089.2009.00543.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,7]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2009,7]]}},"alternative-id":["10.1111\/j.1399-3089.2009.00543.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1399-3089.2009.00543.x","archive":["Portico"],"relation":{},"ISSN":["0908-665X","1399-3089"],"issn-type":[{"value":"0908-665X","type":"print"},{"value":"1399-3089","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,7]]}}}