Role of Intrinsic (Graft) Versus Extrinsic (Host) Factors in the Growth of Transplanted Organs Following Allogeneic and Xenogeneic Transplantation

T. Tanabe, H. Watanabe, J. A. Shah, H. Sahara, A. Shimizu, S. Nomura, A. Asfour, M. Danton, L. Boyd, A. Dardenne Meyers, D. K. Ekanayake-Alper, D. H. Sachs, K. Yamada

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1778-1790
Number of pages13
JournalAmerican Journal of Transplantation
Volume17
Issue number7
DOIs
StatePublished - Jul 2017
Externally publishedYes

Keywords

  • growth and development
  • kidney (allograft) function/dysfunction
  • kidney transplantation/nephrology
  • lung failure/injury
  • lung transplantation/pulmonology
  • organ allocation
  • translational research/science
  • xenotransplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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