title: Role of Intrinsic (Graft) Versus Extrinsic (Host) Factors in the Growth of Transplanted Organs Following Allogeneic and Xenogeneic Transplantation.
abstract: In our studies of life-supporting α-1,3-galactocyltransferase knockout (GalT-KO) pig-to-baboon kidneys, we found that some recipients developed increased serum creatinine with growth of the grafts, without histological or immunological evidence of rejection. We hypothesized that the rapid growth of orthotopic pig grafts in smaller baboon recipients may have led to deterioration of organ function. To test this hypothesis for both kidneys and lungs, we assessed whether the growth of outbred (Yorkshire) organ transplants in miniature swine was regulated by intrinsic (graft) or extrinsic (host environment) factors. Yorkshire kidneys exhibited persistent growth in miniature swine, reaching 3.7 times their initial volume over 3 mo versus 1.2 times for miniature swine kidneys over the same time period. Similar rapid early growth of lung allografts was observed and, in this case, led to organ dysfunction. For xenograft kidneys, a review of our results suggests that there is a threshold for kidney graft volume of 25 cm3/kg of recipient body weight at which cortical ischemia is induced in transplanted GalT-KO kidneys in baboons. These results suggest that intrinsic factors are responsible, at least in part, for growth of donor organs and that this property should be taken into consideration for growth-curve-mismatched transplants, especially for life-supporting organs transplanted into a limited recipient space.
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY.|Transplantation Biology Research Center Laboratory, Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: T
authors.initials: T
authors.lastname: Tanabe
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY.
authors.forename: H
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Transplantation Biology Research Center Laboratory, Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: J A
authors.identifier: http://orcid.org/0000-0003-2097-0656
authors.initials: JA
authors.lastname: Shah
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY.|Division of Organ Replacement and Xenotransplantation Surgery, Center for Advanced Biomedical Science and Swine Research, Kagoshima University, Kagoshima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sahara
authors.affiliation: Department of Analytic Human Pathology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Shimizu
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY.
authors.forename: S
authors.initials: S
authors.lastname: Nomura
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY.
authors.forename: A
authors.initials: A
authors.lastname: Asfour
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY.
authors.forename: M
authors.initials: M
authors.lastname: Danton
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY.
authors.forename: L
authors.initials: L
authors.lastname: Boyd
authors.affiliation: Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation, Orangeburg, NY.
authors.forename: A
authors.initials: A
authors.lastname: Dardenne Meyers
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY.
authors.forename: D K
authors.initials: DK
authors.lastname: Ekanayake-Alper
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY.|Transplantation Biology Research Center Laboratory, Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: D H
authors.initials: DH
authors.lastname: Sachs
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY.|Transplantation Biology Research Center Laboratory, Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: K
authors.initials: K
authors.lastname: Yamada
mesh_terms: D000818:Animals; D005700:Galactosyltransferases; D006085:Graft Survival; D007668:Kidney / Q000201:enzymology / Q000254:growth & development* / Q000473:pathology; D016030:Kidney Transplantation / Q000379:methods*; D008168:Lung / Q000201:enzymology / Q000254:growth & development* / Q000473:pathology; D016040:Lung Transplantation / Q000379:methods*; D008297:Male; D010215:Papio; D013552:Swine; D013556:Swine, Miniature; D014183:Transplantation, Heterologous
chemical_list: D005700:Galactosyltransferases
keywords: growth and development; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; lung failure/injury; lung transplantation/pulmonology; organ allocation; translational research/science; xenotransplantation