The long-term survival of baboon-to-monkey kidney and liver xenografts
: The present study was undertaken to develop an optimum immunosuppressive regimen in baboon‐to‐monkey life‐supporting kidney xenografts. Baseline therapy for all groups include cyclosporine (CsA) and steroids. We compared adding (1) cyclophosphamide (CyP) at dose of 20 mg/kg/day given on post‐oper...
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| Veröffentlicht in: | Xenotransplantation (Københaven) 2003-09, Vol.10 (5), p.398-409 |
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| creator | Zhong, Robert Tucker, Jane Zhang, Zheng Wall, William Grant, David Quan, Douglas Garcia, Bertha Gao, Zu-hua Asfar, Sami Sharpe, Michael Gelb, Adrian Bailey, Michele Stiller, Calvin |
| description | : The present study was undertaken to develop an optimum immunosuppressive regimen in baboon‐to‐monkey life‐supporting kidney xenografts. Baseline therapy for all groups include cyclosporine (CsA) and steroids. We compared adding (1) cyclophosphamide (CyP) at dose of 20 mg/kg/day given on post‐operative day (POD) 0, 2, 5 and 7; (2) mycophenolic mofetil (MMF) at a dose of 40 mg/kg/day by daily gavage; or (3) CyP + rapamycin (Rap). The latter group was divided into high and low dose subgroups. Untreated xenografts were rejected on POD 6, CsA alone treated xenografts survived for 35 days and CsA + CyP treated xenografts survived for 45 days. Adding MMF significantly prolonged mean survival to 111 ± 53 days, but the xenografts eventually developed rejection. Combination therapy including CsA, CyP and Rap reliably prevented xenogenic rejection and achieved a mean survival of 290 ± 30 days. However, high dose CyP + Rap led to high incidence of post‐transplant lymphoproliferation disorders (PTLD), while the incidence of PTLD was significantly less in the low dose subgroup (P |
| doi_str_mv | 10.1034/j.1399-3089.2003.02054.x |
| format | Article |
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Baseline therapy for all groups include cyclosporine (CsA) and steroids. We compared adding (1) cyclophosphamide (CyP) at dose of 20 mg/kg/day given on post‐operative day (POD) 0, 2, 5 and 7; (2) mycophenolic mofetil (MMF) at a dose of 40 mg/kg/day by daily gavage; or (3) CyP + rapamycin (Rap). The latter group was divided into high and low dose subgroups. Untreated xenografts were rejected on POD 6, CsA alone treated xenografts survived for 35 days and CsA + CyP treated xenografts survived for 45 days. Adding MMF significantly prolonged mean survival to 111 ± 53 days, but the xenografts eventually developed rejection. Combination therapy including CsA, CyP and Rap reliably prevented xenogenic rejection and achieved a mean survival of 290 ± 30 days. However, high dose CyP + Rap led to high incidence of post‐transplant lymphoproliferation disorders (PTLD), while the incidence of PTLD was significantly less in the low dose subgroup (P < 0.01). Four animals in this subgroup survived for more than 300 days with normal renal function and histology. In addition, two liver recipients treated with CsA + CyP survived for 91 and 1076 days. We conclude that long‐term survival of kidney or liver xenografts can be achieved in a non‐human concordant xenograft model using currently available immunosuppressive agents.</description><identifier>ISSN: 0908-665X</identifier><identifier>EISSN: 1399-3089</identifier><identifier>DOI: 10.1034/j.1399-3089.2003.02054.x</identifier><identifier>PMID: 12950983</identifier><language>eng</language><publisher>Oxford, UK: Munksgaard International Publishers</publisher><subject>Animals ; Antibodies, Heterophile - blood ; baboon ; Cyclosporine - blood ; Cyclosporine - pharmacokinetics ; Cyclosporine - therapeutic use ; Drug Therapy, Combination ; Female ; Graft Survival - immunology ; Immunosuppressive Agents - blood ; Immunosuppressive Agents - pharmacokinetics ; Immunosuppressive Agents - therapeutic use ; kidney ; Kidney Transplantation - immunology ; liver ; Liver Transplantation - immunology ; Liver Transplantation - pathology ; Macaca fascicularis ; Male ; Methylprednisolone - therapeutic use ; monkey ; Mycophenolic Acid - analogs & derivatives ; Mycophenolic Acid - therapeutic use ; Papio ; rejection ; Sirolimus - therapeutic use ; Time Factors ; Transplantation, Heterologous - immunology ; Transplantation, Heterologous - pathology ; xenotransplantation</subject><ispartof>Xenotransplantation (Københaven), 2003-09, Vol.10 (5), p.398-409</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4374-933cedf4d0d9daa3af9de2365d886e7c18b11522676e3cf823804f7eac02a16c3</citedby><cites>FETCH-LOGICAL-c4374-933cedf4d0d9daa3af9de2365d886e7c18b11522676e3cf823804f7eac02a16c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1034%2Fj.1399-3089.2003.02054.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1034%2Fj.1399-3089.2003.02054.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12950983$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhong, Robert</creatorcontrib><creatorcontrib>Tucker, Jane</creatorcontrib><creatorcontrib>Zhang, Zheng</creatorcontrib><creatorcontrib>Wall, William</creatorcontrib><creatorcontrib>Grant, David</creatorcontrib><creatorcontrib>Quan, Douglas</creatorcontrib><creatorcontrib>Garcia, Bertha</creatorcontrib><creatorcontrib>Gao, Zu-hua</creatorcontrib><creatorcontrib>Asfar, Sami</creatorcontrib><creatorcontrib>Sharpe, Michael</creatorcontrib><creatorcontrib>Gelb, Adrian</creatorcontrib><creatorcontrib>Bailey, Michele</creatorcontrib><creatorcontrib>Stiller, Calvin</creatorcontrib><title>The long-term survival of baboon-to-monkey kidney and liver xenografts</title><title>Xenotransplantation (Københaven)</title><addtitle>Xenotransplantation</addtitle><description>: The present study was undertaken to develop an optimum immunosuppressive regimen in baboon‐to‐monkey life‐supporting kidney xenografts. Baseline therapy for all groups include cyclosporine (CsA) and steroids. We compared adding (1) cyclophosphamide (CyP) at dose of 20 mg/kg/day given on post‐operative day (POD) 0, 2, 5 and 7; (2) mycophenolic mofetil (MMF) at a dose of 40 mg/kg/day by daily gavage; or (3) CyP + rapamycin (Rap). The latter group was divided into high and low dose subgroups. Untreated xenografts were rejected on POD 6, CsA alone treated xenografts survived for 35 days and CsA + CyP treated xenografts survived for 45 days. Adding MMF significantly prolonged mean survival to 111 ± 53 days, but the xenografts eventually developed rejection. Combination therapy including CsA, CyP and Rap reliably prevented xenogenic rejection and achieved a mean survival of 290 ± 30 days. However, high dose CyP + Rap led to high incidence of post‐transplant lymphoproliferation disorders (PTLD), while the incidence of PTLD was significantly less in the low dose subgroup (P < 0.01). Four animals in this subgroup survived for more than 300 days with normal renal function and histology. In addition, two liver recipients treated with CsA + CyP survived for 91 and 1076 days. We conclude that long‐term survival of kidney or liver xenografts can be achieved in a non‐human concordant xenograft model using currently available immunosuppressive agents.</description><subject>Animals</subject><subject>Antibodies, Heterophile - blood</subject><subject>baboon</subject><subject>Cyclosporine - blood</subject><subject>Cyclosporine - pharmacokinetics</subject><subject>Cyclosporine - therapeutic use</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>Graft Survival - immunology</subject><subject>Immunosuppressive Agents - blood</subject><subject>Immunosuppressive Agents - pharmacokinetics</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>kidney</subject><subject>Kidney Transplantation - immunology</subject><subject>liver</subject><subject>Liver Transplantation - immunology</subject><subject>Liver Transplantation - pathology</subject><subject>Macaca fascicularis</subject><subject>Male</subject><subject>Methylprednisolone - therapeutic use</subject><subject>monkey</subject><subject>Mycophenolic Acid - analogs & derivatives</subject><subject>Mycophenolic Acid - therapeutic use</subject><subject>Papio</subject><subject>rejection</subject><subject>Sirolimus - therapeutic use</subject><subject>Time Factors</subject><subject>Transplantation, Heterologous - immunology</subject><subject>Transplantation, Heterologous - pathology</subject><subject>xenotransplantation</subject><issn>0908-665X</issn><issn>1399-3089</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkMlO6zAUQC0EgjL8Asrq7Rw8xI69QULMApVNGXaWG99A2iTm2Wlp_56UVrCE1b2Szz2WDkIJJSklPDuZpJRrjTlROmWE8JQwIrJ0sYUG3w_baEA0UVhK8bKH9mOckJ4USuyiPcq0IFrxAboavUFS-_YVdxCaJM7CvJrbOvFlMrZj71vcedz4dgrLZFq5th-2dUldzSEkC2j9a7BlFw_RTmnrCEebeYAery5H5zf4_uH69vzsHhcZzzOsOS_AlZkjTjtruS21A8alcEpJyAuqxpQKxmQugRelYlyRrMzBFoRZKgt-gP6tve_B_59B7ExTxQLq2rbgZ9HkXFImmPgVpHnPKUl6UK3BIvgYA5TmPVSNDUtDiVnFNhOzampWTc0qtvmKbRb96fHmj9m4AfdzuKnbA6dr4KOqYflnsXm5HLKHfu0FeC2oYgeLb4ENUyNzngvzPLw2T3fsRg8vnsyIfwJSc50a</recordid><startdate>200309</startdate><enddate>200309</enddate><creator>Zhong, Robert</creator><creator>Tucker, Jane</creator><creator>Zhang, Zheng</creator><creator>Wall, William</creator><creator>Grant, David</creator><creator>Quan, Douglas</creator><creator>Garcia, Bertha</creator><creator>Gao, Zu-hua</creator><creator>Asfar, Sami</creator><creator>Sharpe, Michael</creator><creator>Gelb, Adrian</creator><creator>Bailey, Michele</creator><creator>Stiller, Calvin</creator><general>Munksgaard International Publishers</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>200309</creationdate><title>The long-term survival of baboon-to-monkey kidney and liver xenografts</title><author>Zhong, Robert ; Tucker, Jane ; Zhang, Zheng ; Wall, William ; Grant, David ; Quan, Douglas ; Garcia, Bertha ; Gao, Zu-hua ; Asfar, Sami ; Sharpe, Michael ; Gelb, Adrian ; Bailey, Michele ; Stiller, Calvin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4374-933cedf4d0d9daa3af9de2365d886e7c18b11522676e3cf823804f7eac02a16c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Antibodies, Heterophile - blood</topic><topic>baboon</topic><topic>Cyclosporine - blood</topic><topic>Cyclosporine - pharmacokinetics</topic><topic>Cyclosporine - therapeutic use</topic><topic>Drug Therapy, Combination</topic><topic>Female</topic><topic>Graft Survival - immunology</topic><topic>Immunosuppressive Agents - blood</topic><topic>Immunosuppressive Agents - pharmacokinetics</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>kidney</topic><topic>Kidney Transplantation - immunology</topic><topic>liver</topic><topic>Liver Transplantation - immunology</topic><topic>Liver Transplantation - pathology</topic><topic>Macaca fascicularis</topic><topic>Male</topic><topic>Methylprednisolone - therapeutic use</topic><topic>monkey</topic><topic>Mycophenolic Acid - analogs & derivatives</topic><topic>Mycophenolic Acid - therapeutic use</topic><topic>Papio</topic><topic>rejection</topic><topic>Sirolimus - therapeutic use</topic><topic>Time Factors</topic><topic>Transplantation, Heterologous - immunology</topic><topic>Transplantation, Heterologous - pathology</topic><topic>xenotransplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhong, Robert</creatorcontrib><creatorcontrib>Tucker, Jane</creatorcontrib><creatorcontrib>Zhang, Zheng</creatorcontrib><creatorcontrib>Wall, William</creatorcontrib><creatorcontrib>Grant, David</creatorcontrib><creatorcontrib>Quan, Douglas</creatorcontrib><creatorcontrib>Garcia, Bertha</creatorcontrib><creatorcontrib>Gao, Zu-hua</creatorcontrib><creatorcontrib>Asfar, Sami</creatorcontrib><creatorcontrib>Sharpe, Michael</creatorcontrib><creatorcontrib>Gelb, Adrian</creatorcontrib><creatorcontrib>Bailey, Michele</creatorcontrib><creatorcontrib>Stiller, Calvin</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Xenotransplantation (Københaven)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhong, Robert</au><au>Tucker, Jane</au><au>Zhang, Zheng</au><au>Wall, William</au><au>Grant, David</au><au>Quan, Douglas</au><au>Garcia, Bertha</au><au>Gao, Zu-hua</au><au>Asfar, Sami</au><au>Sharpe, Michael</au><au>Gelb, Adrian</au><au>Bailey, Michele</au><au>Stiller, Calvin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The long-term survival of baboon-to-monkey kidney and liver xenografts</atitle><jtitle>Xenotransplantation (Københaven)</jtitle><addtitle>Xenotransplantation</addtitle><date>2003-09</date><risdate>2003</risdate><volume>10</volume><issue>5</issue><spage>398</spage><epage>409</epage><pages>398-409</pages><issn>0908-665X</issn><eissn>1399-3089</eissn><abstract>: The present study was undertaken to develop an optimum immunosuppressive regimen in baboon‐to‐monkey life‐supporting kidney xenografts. Baseline therapy for all groups include cyclosporine (CsA) and steroids. We compared adding (1) cyclophosphamide (CyP) at dose of 20 mg/kg/day given on post‐operative day (POD) 0, 2, 5 and 7; (2) mycophenolic mofetil (MMF) at a dose of 40 mg/kg/day by daily gavage; or (3) CyP + rapamycin (Rap). The latter group was divided into high and low dose subgroups. Untreated xenografts were rejected on POD 6, CsA alone treated xenografts survived for 35 days and CsA + CyP treated xenografts survived for 45 days. Adding MMF significantly prolonged mean survival to 111 ± 53 days, but the xenografts eventually developed rejection. Combination therapy including CsA, CyP and Rap reliably prevented xenogenic rejection and achieved a mean survival of 290 ± 30 days. However, high dose CyP + Rap led to high incidence of post‐transplant lymphoproliferation disorders (PTLD), while the incidence of PTLD was significantly less in the low dose subgroup (P < 0.01). Four animals in this subgroup survived for more than 300 days with normal renal function and histology. In addition, two liver recipients treated with CsA + CyP survived for 91 and 1076 days. We conclude that long‐term survival of kidney or liver xenografts can be achieved in a non‐human concordant xenograft model using currently available immunosuppressive agents.</abstract><cop>Oxford, UK</cop><pub>Munksgaard International Publishers</pub><pmid>12950983</pmid><doi>10.1034/j.1399-3089.2003.02054.x</doi><tpages>12</tpages></addata></record> |
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| subjects | Animals Antibodies, Heterophile - blood baboon Cyclosporine - blood Cyclosporine - pharmacokinetics Cyclosporine - therapeutic use Drug Therapy, Combination Female Graft Survival - immunology Immunosuppressive Agents - blood Immunosuppressive Agents - pharmacokinetics Immunosuppressive Agents - therapeutic use kidney Kidney Transplantation - immunology liver Liver Transplantation - immunology Liver Transplantation - pathology Macaca fascicularis Male Methylprednisolone - therapeutic use monkey Mycophenolic Acid - analogs & derivatives Mycophenolic Acid - therapeutic use Papio rejection Sirolimus - therapeutic use Time Factors Transplantation, Heterologous - immunology Transplantation, Heterologous - pathology xenotransplantation |
| title | The long-term survival of baboon-to-monkey kidney and liver xenografts |
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