Xenotransplantation of canine, bovine, and porcine islets in diabetic rats without immunosuppression
Permselective acrylic membranes were employed to prevent immune rejection of discordant islet xenografts isolated from various large animals. Canine, porcine, and bovine islets were seeded into tubular diffusion chambers and transplanted into the peritoneum of 27 nonimmunosuppressed streptozotocin-i...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1991-12, Vol.88 (24), p.11100-11104 |
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| creator | LANZA, R. P BUTLER, D. H CHICK, W. L BORLAND, K. M STARUK, J. E FAUSTMAN, D. L SOLOMON, B. A MULLER, T. E RUPP, R. G MAKI, T MONACO, A. P |
| description | Permselective acrylic membranes were employed to prevent immune rejection of discordant islet xenografts isolated from various large animals. Canine, porcine, and bovine islets were seeded into tubular diffusion chambers and transplanted into the peritoneum of 27 nonimmunosuppressed streptozotocin-induced diabetic Lewis rats. Six recipients received islet grafts from bovine calves, 7 received grafts from pigs, and 14 received grafts from dogs. Four of the latter were removed at 1 month. In the control group of 10 diabetic rats, 4 received nonencapsulated canine islets, 3 received nonencapsulated bovine islets, and 3 received nonencapsulated porcine islets. Recipients of encapsulated islets promptly dropped from a pretransplantation plasma glucose level of 487 +/- 36 (mean +/- SEM) to 84 +/- 2 (canine), 81 +/- 4 (bovine), and 81 +/- 3 mg/dl (porcine) during the first week. All of the animals sustained these levels for at least 1 month. One rat spontaneously reverted to diabetes at 54 days posttransplantation; 4 other rats became hyperglycemic (glucose, > 600 mg/dl) after membrane removal on day 30. The remaining 22 rats maintained fasting euglycemia for > 10 weeks. In contrast, rats that received nonencapsulated islets became hyperglycemic in < 7 days. Intravenous glucose tolerance test K values (decline in glucose levels, % / min) at 1 month for the canine and bovine encapsulated islet transplant group were 3.5 +/- 0.3 and 3.3 +/- 0.1 compared with 3.3 +/- 0.1 (P = 0.63) and 0.91 +/- 0.1 (P < 0.0001) for normal (n = 4) and diabetic (n = 4) control groups. Morphologic studies of long-term functioning grafts (30-130 days) revealed well-preserved alpha, beta, and delta cells, with varying degrees of granulation. These results demonstrate that immune isolation of islet tissue using permselective artificial membranes can protect discordant islet xenografts from immune rejection in the absence of any immunosuppressive drugs. |
| doi_str_mv | 10.1073/pnas.88.24.11100 |
| format | Article |
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P ; BUTLER, D. H ; CHICK, W. L ; BORLAND, K. M ; STARUK, J. E ; FAUSTMAN, D. L ; SOLOMON, B. A ; MULLER, T. E ; RUPP, R. G ; MAKI, T ; MONACO, A. P</creator><creatorcontrib>LANZA, R. P ; BUTLER, D. H ; CHICK, W. L ; BORLAND, K. M ; STARUK, J. E ; FAUSTMAN, D. L ; SOLOMON, B. A ; MULLER, T. E ; RUPP, R. G ; MAKI, T ; MONACO, A. P ; BioHybrid Technologies, Inc., Shrewsbury, MA</creatorcontrib><description>Permselective acrylic membranes were employed to prevent immune rejection of discordant islet xenografts isolated from various large animals. Canine, porcine, and bovine islets were seeded into tubular diffusion chambers and transplanted into the peritoneum of 27 nonimmunosuppressed streptozotocin-induced diabetic Lewis rats. Six recipients received islet grafts from bovine calves, 7 received grafts from pigs, and 14 received grafts from dogs. Four of the latter were removed at 1 month. In the control group of 10 diabetic rats, 4 received nonencapsulated canine islets, 3 received nonencapsulated bovine islets, and 3 received nonencapsulated porcine islets. Recipients of encapsulated islets promptly dropped from a pretransplantation plasma glucose level of 487 +/- 36 (mean +/- SEM) to 84 +/- 2 (canine), 81 +/- 4 (bovine), and 81 +/- 3 mg/dl (porcine) during the first week. All of the animals sustained these levels for at least 1 month. One rat spontaneously reverted to diabetes at 54 days posttransplantation; 4 other rats became hyperglycemic (glucose, > 600 mg/dl) after membrane removal on day 30. The remaining 22 rats maintained fasting euglycemia for > 10 weeks. In contrast, rats that received nonencapsulated islets became hyperglycemic in < 7 days. Intravenous glucose tolerance test K values (decline in glucose levels, % / min) at 1 month for the canine and bovine encapsulated islet transplant group were 3.5 +/- 0.3 and 3.3 +/- 0.1 compared with 3.3 +/- 0.1 (P = 0.63) and 0.91 +/- 0.1 (P < 0.0001) for normal (n = 4) and diabetic (n = 4) control groups. Morphologic studies of long-term functioning grafts (30-130 days) revealed well-preserved alpha, beta, and delta cells, with varying degrees of granulation. These results demonstrate that immune isolation of islet tissue using permselective artificial membranes can protect discordant islet xenografts from immune rejection in the absence of any immunosuppressive drugs.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.88.24.11100</identifier><identifier>PMID: 1763025</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>Analysis of Variance ; Animals ; Biological and medical sciences ; Blood Glucose - metabolism ; bovin ; Canines ; Cattle ; cerdo ; chien ; ciencias medicas ; control de enfermedades ; controle de maladies ; diabete ; Diabetes ; Diabetes complications ; Diabetes mellitus ; Diabetes Mellitus, Experimental - blood ; Diabetes Mellitus, Experimental - surgery ; disease control ; Dogs ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; ganado bovino ; Glucose - pharmacology ; Heterologous transplantation ; immunodepression ; Immunoenzyme Techniques ; Immunosuppression ; inmunodepresion ; Insulin ; Insulin - analysis ; Insulin - metabolism ; Insulin Secretion ; investigacion ; Islets of Langerhans - cytology ; Islets of Langerhans - drug effects ; Islets of Langerhans - metabolism ; Islets of Langerhans Transplantation - immunology ; Islets of Langerhans Transplantation - physiology ; medical sciences ; P branes ; pancreas ; perro ; porcin ; rat ; rata ; Rats ; Rats, Inbred Lew ; recherche ; sciences medicales ; Swine ; Tissue, organ and graft immunology ; Transplantation ; Transplantation, Heterologous - immunology ; Transplantation, Heterologous - physiology ; trasplantes ; Ungulates</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1991-12, Vol.88 (24), p.11100-11104</ispartof><rights>Copyright 1991 The National Academy of Sciences of the United States of America</rights><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c616t-c0a0783de84c19a8d8151aaec0620483e7d8786ae34efeb0121c94d1037b69873</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/88/24.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2359191$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2359191$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5225952$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1763025$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>LANZA, R. P</creatorcontrib><creatorcontrib>BUTLER, D. H</creatorcontrib><creatorcontrib>CHICK, W. L</creatorcontrib><creatorcontrib>BORLAND, K. M</creatorcontrib><creatorcontrib>STARUK, J. E</creatorcontrib><creatorcontrib>FAUSTMAN, D. L</creatorcontrib><creatorcontrib>SOLOMON, B. A</creatorcontrib><creatorcontrib>MULLER, T. E</creatorcontrib><creatorcontrib>RUPP, R. G</creatorcontrib><creatorcontrib>MAKI, T</creatorcontrib><creatorcontrib>MONACO, A. P</creatorcontrib><creatorcontrib>BioHybrid Technologies, Inc., Shrewsbury, MA</creatorcontrib><title>Xenotransplantation of canine, bovine, and porcine islets in diabetic rats without immunosuppression</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Permselective acrylic membranes were employed to prevent immune rejection of discordant islet xenografts isolated from various large animals. Canine, porcine, and bovine islets were seeded into tubular diffusion chambers and transplanted into the peritoneum of 27 nonimmunosuppressed streptozotocin-induced diabetic Lewis rats. Six recipients received islet grafts from bovine calves, 7 received grafts from pigs, and 14 received grafts from dogs. Four of the latter were removed at 1 month. In the control group of 10 diabetic rats, 4 received nonencapsulated canine islets, 3 received nonencapsulated bovine islets, and 3 received nonencapsulated porcine islets. Recipients of encapsulated islets promptly dropped from a pretransplantation plasma glucose level of 487 +/- 36 (mean +/- SEM) to 84 +/- 2 (canine), 81 +/- 4 (bovine), and 81 +/- 3 mg/dl (porcine) during the first week. All of the animals sustained these levels for at least 1 month. One rat spontaneously reverted to diabetes at 54 days posttransplantation; 4 other rats became hyperglycemic (glucose, > 600 mg/dl) after membrane removal on day 30. The remaining 22 rats maintained fasting euglycemia for > 10 weeks. In contrast, rats that received nonencapsulated islets became hyperglycemic in < 7 days. Intravenous glucose tolerance test K values (decline in glucose levels, % / min) at 1 month for the canine and bovine encapsulated islet transplant group were 3.5 +/- 0.3 and 3.3 +/- 0.1 compared with 3.3 +/- 0.1 (P = 0.63) and 0.91 +/- 0.1 (P < 0.0001) for normal (n = 4) and diabetic (n = 4) control groups. Morphologic studies of long-term functioning grafts (30-130 days) revealed well-preserved alpha, beta, and delta cells, with varying degrees of granulation. These results demonstrate that immune isolation of islet tissue using permselective artificial membranes can protect discordant islet xenografts from immune rejection in the absence of any immunosuppressive drugs.</description><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood Glucose - metabolism</subject><subject>bovin</subject><subject>Canines</subject><subject>Cattle</subject><subject>cerdo</subject><subject>chien</subject><subject>ciencias medicas</subject><subject>control de enfermedades</subject><subject>controle de maladies</subject><subject>diabete</subject><subject>Diabetes</subject><subject>Diabetes complications</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Experimental - blood</subject><subject>Diabetes Mellitus, Experimental - surgery</subject><subject>disease control</subject><subject>Dogs</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>ganado bovino</subject><subject>Glucose - pharmacology</subject><subject>Heterologous transplantation</subject><subject>immunodepression</subject><subject>Immunoenzyme Techniques</subject><subject>Immunosuppression</subject><subject>inmunodepresion</subject><subject>Insulin</subject><subject>Insulin - analysis</subject><subject>Insulin - metabolism</subject><subject>Insulin Secretion</subject><subject>investigacion</subject><subject>Islets of Langerhans - cytology</subject><subject>Islets of Langerhans - drug effects</subject><subject>Islets of Langerhans - metabolism</subject><subject>Islets of Langerhans Transplantation - immunology</subject><subject>Islets of Langerhans Transplantation - physiology</subject><subject>medical sciences</subject><subject>P branes</subject><subject>pancreas</subject><subject>perro</subject><subject>porcin</subject><subject>rat</subject><subject>rata</subject><subject>Rats</subject><subject>Rats, Inbred Lew</subject><subject>recherche</subject><subject>sciences medicales</subject><subject>Swine</subject><subject>Tissue, organ and graft immunology</subject><subject>Transplantation</subject><subject>Transplantation, Heterologous - immunology</subject><subject>Transplantation, Heterologous - physiology</subject><subject>trasplantes</subject><subject>Ungulates</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtv1DAUhS0EKkNhz4JHFgixIMP1I7EtsUEVL6kSC6jEznIcp3WV2MF2Cvx7PM0w0A2sruzz3edB6CGGLQZOX81ep60QW8K2GGOAW2iDQeK6ZRJuow0A4bVghN1F91K6BADZCDhCR5i3FEizQf1X60OO2qd51D7r7IKvwlAZ7Z23L6suXF1H7ftqDtGUR-XSaHOqnK96pzubnamiLh_fXb4IS67cNC0-pGWeo02pFLyP7gx6TPbBPh6js3dvv5x8qE8_vf948ua0Ni1uc21AAxe0t4IZLLXoBW6w1tZAS4AJankvuGi1pcwOtgNMsJGsx0B510rB6TF6vdadl26yvbG-bDaqObpJx58qaKduKt5dqPNwpRoKApf05_v0GL4tNmU1uWTsWA5jw5IUJ40glLL_grgFDkyKAsIKmhhSinY4zIJB7QxUOwOVEIowdW1gSXn89w5_ElbHiv5sr-tk9DgU64xLB6whpJENKdjTPbZr8Fu92ejFvwk1LOOY7Y9c0EcreplyiAeW0EZiubvbk1UedFD6PJZxzj5jKQkAl0IA_QX95dEE</recordid><startdate>19911215</startdate><enddate>19911215</enddate><creator>LANZA, R. P</creator><creator>BUTLER, D. H</creator><creator>CHICK, W. L</creator><creator>BORLAND, K. M</creator><creator>STARUK, J. E</creator><creator>FAUSTMAN, D. L</creator><creator>SOLOMON, B. A</creator><creator>MULLER, T. E</creator><creator>RUPP, R. G</creator><creator>MAKI, T</creator><creator>MONACO, A. P</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><scope>FBQ</scope><scope>IQODW</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><scope>5PM</scope></search><sort><creationdate>19911215</creationdate><title>Xenotransplantation of canine, bovine, and porcine islets in diabetic rats without immunosuppression</title><author>LANZA, R. P ; BUTLER, D. H ; CHICK, W. L ; BORLAND, K. M ; STARUK, J. E ; FAUSTMAN, D. L ; SOLOMON, B. A ; MULLER, T. E ; RUPP, R. G ; MAKI, T ; MONACO, A. P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c616t-c0a0783de84c19a8d8151aaec0620483e7d8786ae34efeb0121c94d1037b69873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood Glucose - metabolism</topic><topic>bovin</topic><topic>Canines</topic><topic>Cattle</topic><topic>cerdo</topic><topic>chien</topic><topic>ciencias medicas</topic><topic>control de enfermedades</topic><topic>controle de maladies</topic><topic>diabete</topic><topic>Diabetes</topic><topic>Diabetes complications</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Experimental - blood</topic><topic>Diabetes Mellitus, Experimental - surgery</topic><topic>disease control</topic><topic>Dogs</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>ganado bovino</topic><topic>Glucose - pharmacology</topic><topic>Heterologous transplantation</topic><topic>immunodepression</topic><topic>Immunoenzyme Techniques</topic><topic>Immunosuppression</topic><topic>inmunodepresion</topic><topic>Insulin</topic><topic>Insulin - analysis</topic><topic>Insulin - metabolism</topic><topic>Insulin Secretion</topic><topic>investigacion</topic><topic>Islets of Langerhans - cytology</topic><topic>Islets of Langerhans - drug effects</topic><topic>Islets of Langerhans - metabolism</topic><topic>Islets of Langerhans Transplantation - immunology</topic><topic>Islets of Langerhans Transplantation - physiology</topic><topic>medical sciences</topic><topic>P branes</topic><topic>pancreas</topic><topic>perro</topic><topic>porcin</topic><topic>rat</topic><topic>rata</topic><topic>Rats</topic><topic>Rats, Inbred Lew</topic><topic>recherche</topic><topic>sciences medicales</topic><topic>Swine</topic><topic>Tissue, organ and graft immunology</topic><topic>Transplantation</topic><topic>Transplantation, Heterologous - immunology</topic><topic>Transplantation, Heterologous - physiology</topic><topic>trasplantes</topic><topic>Ungulates</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>LANZA, R. P</creatorcontrib><creatorcontrib>BUTLER, D. H</creatorcontrib><creatorcontrib>CHICK, W. L</creatorcontrib><creatorcontrib>BORLAND, K. M</creatorcontrib><creatorcontrib>STARUK, J. E</creatorcontrib><creatorcontrib>FAUSTMAN, D. L</creatorcontrib><creatorcontrib>SOLOMON, B. A</creatorcontrib><creatorcontrib>MULLER, T. E</creatorcontrib><creatorcontrib>RUPP, R. G</creatorcontrib><creatorcontrib>MAKI, T</creatorcontrib><creatorcontrib>MONACO, A. P</creatorcontrib><creatorcontrib>BioHybrid Technologies, Inc., Shrewsbury, MA</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>LANZA, R. P</au><au>BUTLER, D. H</au><au>CHICK, W. L</au><au>BORLAND, K. M</au><au>STARUK, J. E</au><au>FAUSTMAN, D. L</au><au>SOLOMON, B. A</au><au>MULLER, T. E</au><au>RUPP, R. G</au><au>MAKI, T</au><au>MONACO, A. P</au><aucorp>BioHybrid Technologies, Inc., Shrewsbury, MA</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Xenotransplantation of canine, bovine, and porcine islets in diabetic rats without immunosuppression</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1991-12-15</date><risdate>1991</risdate><volume>88</volume><issue>24</issue><spage>11100</spage><epage>11104</epage><pages>11100-11104</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>Permselective acrylic membranes were employed to prevent immune rejection of discordant islet xenografts isolated from various large animals. Canine, porcine, and bovine islets were seeded into tubular diffusion chambers and transplanted into the peritoneum of 27 nonimmunosuppressed streptozotocin-induced diabetic Lewis rats. Six recipients received islet grafts from bovine calves, 7 received grafts from pigs, and 14 received grafts from dogs. Four of the latter were removed at 1 month. In the control group of 10 diabetic rats, 4 received nonencapsulated canine islets, 3 received nonencapsulated bovine islets, and 3 received nonencapsulated porcine islets. Recipients of encapsulated islets promptly dropped from a pretransplantation plasma glucose level of 487 +/- 36 (mean +/- SEM) to 84 +/- 2 (canine), 81 +/- 4 (bovine), and 81 +/- 3 mg/dl (porcine) during the first week. All of the animals sustained these levels for at least 1 month. One rat spontaneously reverted to diabetes at 54 days posttransplantation; 4 other rats became hyperglycemic (glucose, > 600 mg/dl) after membrane removal on day 30. The remaining 22 rats maintained fasting euglycemia for > 10 weeks. In contrast, rats that received nonencapsulated islets became hyperglycemic in < 7 days. Intravenous glucose tolerance test K values (decline in glucose levels, % / min) at 1 month for the canine and bovine encapsulated islet transplant group were 3.5 +/- 0.3 and 3.3 +/- 0.1 compared with 3.3 +/- 0.1 (P = 0.63) and 0.91 +/- 0.1 (P < 0.0001) for normal (n = 4) and diabetic (n = 4) control groups. Morphologic studies of long-term functioning grafts (30-130 days) revealed well-preserved alpha, beta, and delta cells, with varying degrees of granulation. These results demonstrate that immune isolation of islet tissue using permselective artificial membranes can protect discordant islet xenografts from immune rejection in the absence of any immunosuppressive drugs.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>1763025</pmid><doi>10.1073/pnas.88.24.11100</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1991-12, Vol.88 (24), p.11100-11104 |
| issn | 0027-8424 1091-6490 |
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| subjects | Analysis of Variance Animals Biological and medical sciences Blood Glucose - metabolism bovin Canines Cattle cerdo chien ciencias medicas control de enfermedades controle de maladies diabete Diabetes Diabetes complications Diabetes mellitus Diabetes Mellitus, Experimental - blood Diabetes Mellitus, Experimental - surgery disease control Dogs Fundamental and applied biological sciences. Psychology Fundamental immunology ganado bovino Glucose - pharmacology Heterologous transplantation immunodepression Immunoenzyme Techniques Immunosuppression inmunodepresion Insulin Insulin - analysis Insulin - metabolism Insulin Secretion investigacion Islets of Langerhans - cytology Islets of Langerhans - drug effects Islets of Langerhans - metabolism Islets of Langerhans Transplantation - immunology Islets of Langerhans Transplantation - physiology medical sciences P branes pancreas perro porcin rat rata Rats Rats, Inbred Lew recherche sciences medicales Swine Tissue, organ and graft immunology Transplantation Transplantation, Heterologous - immunology Transplantation, Heterologous - physiology trasplantes Ungulates |
| title | Xenotransplantation of canine, bovine, and porcine islets in diabetic rats without immunosuppression |
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