TY - JOUR
T1 - Role of Intrinsic (Graft) Versus Extrinsic (Host) Factors in the Growth of Transplanted Organs Following Allogeneic and Xenogeneic Transplantation
AU - Tanabe, T.
AU - Watanabe, H.
AU - Shah, J. A.
AU - Sahara, H.
AU - Shimizu, A.
AU - Nomura, S.
AU - Asfour, A.
AU - Danton, M.
AU - Boyd, L.
AU - Dardenne Meyers, A.
AU - Ekanayake-Alper, D. K.
AU - Sachs, D. H.
AU - Yamada, K.
N1 - Funding Information:
The authors would like to thank Dr. Masayuki Tasaki for his helpful advice and review of this manuscript. We thank Bristol-Myers Squibb for providing CTLA4-Ig, Genzyme for rabbit ATG and Genentech for rituximab. This research was supported by NIH grant 2P01AI45897-11A1 and by a Sponsored Research Agreement from Lung Biotech, PBC.
Publisher Copyright:
© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons
PY - 2017/7
Y1 - 2017/7
N2 - 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.
AB - 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.
KW - growth and development
KW - kidney (allograft) function/dysfunction
KW - kidney transplantation/nephrology
KW - lung failure/injury
KW - lung transplantation/pulmonology
KW - organ allocation
KW - translational research/science
KW - xenotransplantation
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U2 - 10.1111/ajt.14210
DO - 10.1111/ajt.14210
M3 - Article
C2 - 28117931
AN - SCOPUS:85014247427
SN - 1600-6135
VL - 17
SP - 1778
EP - 1790
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 7
ER -