Pre-clinical model of composite foetal pig pancreas fragment/renal xenotransplantation to treat renal failure and diabetes

Hawthorne WJ, Simond DM, Stokes R, Patel AT, Walters S, Burgess J, O’Connell PJ. Pre‐clinical model of composite foetal pig pancreas fragment/renal xenotransplantation to treat renal failure and diabetes. Xenotransplantation 2011; 18: 390–399. © 2011 John Wiley & Sons A/S. :  Background:  Develo...

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Veröffentlicht in:Xenotransplantation (Københaven) 2011-11, Vol.18 (6), p.390-399
Hauptverfasser: Hawthorne, Wayne J., Simond, Denbigh M., Stokes, Rebecca, Patel, Anita T., Walters, Stacey, Burgess, Jane, O'Connell, Philip J.
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container_end_page 399
container_issue 6
container_start_page 390
container_title Xenotransplantation (Københaven)
container_volume 18
creator Hawthorne, Wayne J.
Simond, Denbigh M.
Stokes, Rebecca
Patel, Anita T.
Walters, Stacey
Burgess, Jane
O'Connell, Philip J.
description Hawthorne WJ, Simond DM, Stokes R, Patel AT, Walters S, Burgess J, O’Connell PJ. Pre‐clinical model of composite foetal pig pancreas fragment/renal xenotransplantation to treat renal failure and diabetes. Xenotransplantation 2011; 18: 390–399. © 2011 John Wiley & Sons A/S. :  Background:  Development of a limitless source of β cells for xenotransplantation into patients suffering type 1 diabetes and renal failure that can control their diabetes and provide normal renal function in one procedure would be a major achievement. For the islet tissue to survive transplantation, as an islet‐kidney composite graft this would have significant advantages. It would simplify the surgical procedure; remove the complications caused by the exocrine pancreas whilst reversing diabetes and uraemia. It was our hypothesis that a composite foetal porcine pancreas fragment (FPPF)/renal graft could achieve these objectives in a large pre‐clinical animal model as a means to establish whether this would be feasible before moving to the clinic. Methods:  Inbred ‘Westran’ pig FPPF were transplanted under the kidney capsule of syngeneic Westran pig recipients without immunosuppression. Following maturation of the FPPF under the renal subcapsular space of this recipient, this kidney bearing the composite FPPF piggyback graft was removed and transplanted into another nephrectomized and pancreatectomized recipient to demonstrate function. Results:  Under the kidney capsule of the first transplant group (n = 6), the FPPF‐transplanted tissue developed and matured to form islet cell nests. These composite FPPF/renal grafts were then successfully removed and transplanted into the second functional assessment recipient group. This second group of six composite FPPF/renal‐grafted pigs had normal renal function for more than 44 days and normal glucose homoeostasis without exogenous insulin as assessed by normal glucose tolerance tests, K values and normal glucagon secretion. Histological analysis showed despite the ischaemic insult during the composite kidney transplant procedure, there was appropriate development of islet‐like structures up to and beyond 224 days after the original transplantation under the kidney capsule. Conclusions:  This study shows that the use of composite FPPF/renal grafts can cure both diabetes and renal failure with a single‐transplant procedure. Using such composite grafts for xenotransplantation would simplify the surgical procedure and protect the islet graft from
doi_str_mv 10.1111/j.1399-3089.2011.00681.x
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Pre‐clinical model of composite foetal pig pancreas fragment/renal xenotransplantation to treat renal failure and diabetes. Xenotransplantation 2011; 18: 390–399. © 2011 John Wiley &amp; Sons A/S. :  Background:  Development of a limitless source of β cells for xenotransplantation into patients suffering type 1 diabetes and renal failure that can control their diabetes and provide normal renal function in one procedure would be a major achievement. For the islet tissue to survive transplantation, as an islet‐kidney composite graft this would have significant advantages. It would simplify the surgical procedure; remove the complications caused by the exocrine pancreas whilst reversing diabetes and uraemia. It was our hypothesis that a composite foetal porcine pancreas fragment (FPPF)/renal graft could achieve these objectives in a large pre‐clinical animal model as a means to establish whether this would be feasible before moving to the clinic. Methods:  Inbred ‘Westran’ pig FPPF were transplanted under the kidney capsule of syngeneic Westran pig recipients without immunosuppression. Following maturation of the FPPF under the renal subcapsular space of this recipient, this kidney bearing the composite FPPF piggyback graft was removed and transplanted into another nephrectomized and pancreatectomized recipient to demonstrate function. Results:  Under the kidney capsule of the first transplant group (n = 6), the FPPF‐transplanted tissue developed and matured to form islet cell nests. These composite FPPF/renal grafts were then successfully removed and transplanted into the second functional assessment recipient group. This second group of six composite FPPF/renal‐grafted pigs had normal renal function for more than 44 days and normal glucose homoeostasis without exogenous insulin as assessed by normal glucose tolerance tests, K values and normal glucagon secretion. Histological analysis showed despite the ischaemic insult during the composite kidney transplant procedure, there was appropriate development of islet‐like structures up to and beyond 224 days after the original transplantation under the kidney capsule. Conclusions:  This study shows that the use of composite FPPF/renal grafts can cure both diabetes and renal failure with a single‐transplant procedure. Using such composite grafts for xenotransplantation would simplify the surgical procedure and protect the islet graft from the immediate innate immune response.</description><identifier>ISSN: 0908-665X</identifier><identifier>EISSN: 1399-3089</identifier><identifier>DOI: 10.1111/j.1399-3089.2011.00681.x</identifier><identifier>PMID: 22168145</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>allografts ; Animals ; Diabetes Mellitus, Type 1 - surgery ; Fetal Tissue Transplantation - methods ; Fetus - anatomy &amp; histology ; foetal pig pancreas fragment ; Glucose Tolerance Test ; inbred pig ; islet cell transplantation ; Islets of Langerhans Transplantation - methods ; kidney transplantation ; Kidney Transplantation - methods ; Pancreas - anatomy &amp; histology ; pancreatectomy ; Renal Insufficiency - surgery ; simultaneous pancreas and kidney transplant ; Swine ; type 1 diabetes ; xenotransplantation</subject><ispartof>Xenotransplantation (Københaven), 2011-11, Vol.18 (6), p.390-399</ispartof><rights>2011 John Wiley &amp; Sons A/S</rights><rights>2011 John Wiley &amp; Sons A/S.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4381-663bcaa85206a5a98841832898c59f8c9ff00c5a1d6010cb696fb58f010d32ff3</citedby><cites>FETCH-LOGICAL-c4381-663bcaa85206a5a98841832898c59f8c9ff00c5a1d6010cb696fb58f010d32ff3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1399-3089.2011.00681.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1399-3089.2011.00681.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22168145$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hawthorne, Wayne J.</creatorcontrib><creatorcontrib>Simond, Denbigh M.</creatorcontrib><creatorcontrib>Stokes, Rebecca</creatorcontrib><creatorcontrib>Patel, Anita T.</creatorcontrib><creatorcontrib>Walters, Stacey</creatorcontrib><creatorcontrib>Burgess, Jane</creatorcontrib><creatorcontrib>O'Connell, Philip J.</creatorcontrib><title>Pre-clinical model of composite foetal pig pancreas fragment/renal xenotransplantation to treat renal failure and diabetes</title><title>Xenotransplantation (Københaven)</title><addtitle>Xenotransplantation</addtitle><description>Hawthorne WJ, Simond DM, Stokes R, Patel AT, Walters S, Burgess J, O’Connell PJ. Pre‐clinical model of composite foetal pig pancreas fragment/renal xenotransplantation to treat renal failure and diabetes. Xenotransplantation 2011; 18: 390–399. © 2011 John Wiley &amp; Sons A/S. :  Background:  Development of a limitless source of β cells for xenotransplantation into patients suffering type 1 diabetes and renal failure that can control their diabetes and provide normal renal function in one procedure would be a major achievement. For the islet tissue to survive transplantation, as an islet‐kidney composite graft this would have significant advantages. It would simplify the surgical procedure; remove the complications caused by the exocrine pancreas whilst reversing diabetes and uraemia. It was our hypothesis that a composite foetal porcine pancreas fragment (FPPF)/renal graft could achieve these objectives in a large pre‐clinical animal model as a means to establish whether this would be feasible before moving to the clinic. Methods:  Inbred ‘Westran’ pig FPPF were transplanted under the kidney capsule of syngeneic Westran pig recipients without immunosuppression. Following maturation of the FPPF under the renal subcapsular space of this recipient, this kidney bearing the composite FPPF piggyback graft was removed and transplanted into another nephrectomized and pancreatectomized recipient to demonstrate function. Results:  Under the kidney capsule of the first transplant group (n = 6), the FPPF‐transplanted tissue developed and matured to form islet cell nests. These composite FPPF/renal grafts were then successfully removed and transplanted into the second functional assessment recipient group. This second group of six composite FPPF/renal‐grafted pigs had normal renal function for more than 44 days and normal glucose homoeostasis without exogenous insulin as assessed by normal glucose tolerance tests, K values and normal glucagon secretion. Histological analysis showed despite the ischaemic insult during the composite kidney transplant procedure, there was appropriate development of islet‐like structures up to and beyond 224 days after the original transplantation under the kidney capsule. Conclusions:  This study shows that the use of composite FPPF/renal grafts can cure both diabetes and renal failure with a single‐transplant procedure. Using such composite grafts for xenotransplantation would simplify the surgical procedure and protect the islet graft from the immediate innate immune response.</description><subject>allografts</subject><subject>Animals</subject><subject>Diabetes Mellitus, Type 1 - surgery</subject><subject>Fetal Tissue Transplantation - methods</subject><subject>Fetus - anatomy &amp; histology</subject><subject>foetal pig pancreas fragment</subject><subject>Glucose Tolerance Test</subject><subject>inbred pig</subject><subject>islet cell transplantation</subject><subject>Islets of Langerhans Transplantation - methods</subject><subject>kidney transplantation</subject><subject>Kidney Transplantation - methods</subject><subject>Pancreas - anatomy &amp; histology</subject><subject>pancreatectomy</subject><subject>Renal Insufficiency - surgery</subject><subject>simultaneous pancreas and kidney transplant</subject><subject>Swine</subject><subject>type 1 diabetes</subject><subject>xenotransplantation</subject><issn>0908-665X</issn><issn>1399-3089</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU9v1DAQxS0EokvhKyDf4JLUjuOsLXFB2z9UqgoSIPZmOc648pLEwfaKLZ8ep2n3iPBlbL3fG4_mIYQpKWk-Z7uSMikLRoQsK0JpSUgjaHl4hlZH4TlaEUlE0TR8e4JexbgjhDAu-Et0UlU08zVfoT9fAhSmd6MzuseD76DH3mLjh8lHlwBbDykrk7vDkx5NAB2xDfpugDGdBRizdoDRp6DHOPV6TDo5P-Lkccpswgtitev3AbAeO9w53UKC-Bq9sLqP8OaxnqLvlxffNp-Km89X15uPN4WpmaB5ftYarQWvSKO5lkLUVLBKSGG4tMJIawkxXNOuIZSYtpGNbbmw-dGxylp2it4tfafgf-0hJjW4aKDPw4LfRyUplfWa1U0m3_-TnHcrCaNsRsWCmuBjDGDVFNygw72iRM0Zqd0DruYo1JyReshIHbL17eMv-3aA7mh8CiUDHxbgt-vh_r8bq-3Fbb5ke7HYXUxwONp1-KmaNVtz9eP2ShGxrTeX_Fx9ZX8BCL-wPQ</recordid><startdate>201111</startdate><enddate>201111</enddate><creator>Hawthorne, Wayne J.</creator><creator>Simond, Denbigh M.</creator><creator>Stokes, Rebecca</creator><creator>Patel, Anita T.</creator><creator>Walters, Stacey</creator><creator>Burgess, Jane</creator><creator>O'Connell, Philip J.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201111</creationdate><title>Pre-clinical model of composite foetal pig pancreas fragment/renal xenotransplantation to treat renal failure and diabetes</title><author>Hawthorne, Wayne J. ; 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Pre‐clinical model of composite foetal pig pancreas fragment/renal xenotransplantation to treat renal failure and diabetes. Xenotransplantation 2011; 18: 390–399. © 2011 John Wiley &amp; Sons A/S. :  Background:  Development of a limitless source of β cells for xenotransplantation into patients suffering type 1 diabetes and renal failure that can control their diabetes and provide normal renal function in one procedure would be a major achievement. For the islet tissue to survive transplantation, as an islet‐kidney composite graft this would have significant advantages. It would simplify the surgical procedure; remove the complications caused by the exocrine pancreas whilst reversing diabetes and uraemia. It was our hypothesis that a composite foetal porcine pancreas fragment (FPPF)/renal graft could achieve these objectives in a large pre‐clinical animal model as a means to establish whether this would be feasible before moving to the clinic. Methods:  Inbred ‘Westran’ pig FPPF were transplanted under the kidney capsule of syngeneic Westran pig recipients without immunosuppression. Following maturation of the FPPF under the renal subcapsular space of this recipient, this kidney bearing the composite FPPF piggyback graft was removed and transplanted into another nephrectomized and pancreatectomized recipient to demonstrate function. Results:  Under the kidney capsule of the first transplant group (n = 6), the FPPF‐transplanted tissue developed and matured to form islet cell nests. These composite FPPF/renal grafts were then successfully removed and transplanted into the second functional assessment recipient group. This second group of six composite FPPF/renal‐grafted pigs had normal renal function for more than 44 days and normal glucose homoeostasis without exogenous insulin as assessed by normal glucose tolerance tests, K values and normal glucagon secretion. Histological analysis showed despite the ischaemic insult during the composite kidney transplant procedure, there was appropriate development of islet‐like structures up to and beyond 224 days after the original transplantation under the kidney capsule. Conclusions:  This study shows that the use of composite FPPF/renal grafts can cure both diabetes and renal failure with a single‐transplant procedure. Using such composite grafts for xenotransplantation would simplify the surgical procedure and protect the islet graft from the immediate innate immune response.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>22168145</pmid><doi>10.1111/j.1399-3089.2011.00681.x</doi><tpages>10</tpages></addata></record>
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1399-3089
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source MEDLINE; Access via Wiley Online Library
subjects allografts
Animals
Diabetes Mellitus, Type 1 - surgery
Fetal Tissue Transplantation - methods
Fetus - anatomy & histology
foetal pig pancreas fragment
Glucose Tolerance Test
inbred pig
islet cell transplantation
Islets of Langerhans Transplantation - methods
kidney transplantation
Kidney Transplantation - methods
Pancreas - anatomy & histology
pancreatectomy
Renal Insufficiency - surgery
simultaneous pancreas and kidney transplant
Swine
type 1 diabetes
xenotransplantation
title Pre-clinical model of composite foetal pig pancreas fragment/renal xenotransplantation to treat renal failure and diabetes
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