Shah Jigesh A, Tanabe Tatsu, Yamada Kazuhiko
Department of Surgery, Transplantation Biology Research Center Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, USA.
Columbia Center for Translational Immunology, Columbia University Medical Center, New York, USA.
J Immunobiol. 2017 Jun;2(2). doi: 10.4172/2476-1966.1000122. Epub 2017 May 2.
Shortages in the availability of transplantable organs have forced the transplant community to seek alternative methods to increase the supply of available organs. In our recent study following α-1,3-galactocyltransferase knockout (GalT-KO) pig-to-baboon kidney xenotransplantation, we found that certain recipients developed increased serum creatinine, possibly due to the rapid growth of orthotopic pig grafts in smaller baboon recipients. To test our hypothesis, we assessed whether the growth of outbred (Yorkshire) organ transplants (kidney and lung) in miniature swine was regulated by intrinsic (graft) factors. Yorkshire kidneys reached 3.7× their initial volume over 3 months 1.2× for miniature swine kidneys over a similar time period. A similar pattern was seen in porcine lung allografts as well. Following xenotransplantation, a review of our results suggests that there is a threshold for kidney graft volume of 25 cm/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 in part responsible for the growth of donor organs and this should be taken into consideration for growth-curve-mismatched transplants.
可移植器官供应短缺迫使移植界寻求增加可用器官供应的替代方法。在我们最近一项关于α-1,3-半乳糖基转移酶敲除(GalT-KO)猪到狒狒肾脏异种移植的研究中,我们发现某些受体血清肌酐升高,这可能是由于在较小的狒狒受体中,原位猪移植物快速生长所致。为了验证我们的假设,我们评估了小型猪中外来(约克夏)器官移植(肾脏和肺)的生长是否受内在(移植物)因素调控。约克夏肾脏在3个月内体积增长至初始体积的3.7倍,而小型猪肾脏在相似时间段内增长至1.2倍。猪肺同种异体移植中也观察到类似模式。异种移植后,对我们结果的回顾表明,对于狒狒体内移植的GalT-KO肾脏,当肾脏移植物体积达到25 cm³/kg受体体重时,会引发皮质缺血。这些结果表明,内在因素在一定程度上决定了供体器官的生长,对于生长曲线不匹配的移植应考虑这一点。