Small-for-size liver transplanted into larger recipient: A model of hepatic regeneration

Abstract

Orthotopic liver transplantation was performed in 60 recipient rats weighing 200 to 250 gm. Sixty rats of the same strain were used as liver donors, 30 weighing 100 to 140 gm (small for size) and the other 30 weighing 200 to 250 gm (same size). Mter 1, 2, 3, 4, 7 and 14 days (n = 5 each) DNA synthesis, nuclear thymidine labeling and mitoses were increased in both the smallfor-size and same-size groups, but significantly more in the former. These changes were maximal after 48 to 72 hr, similar to but later than the well-known regeneration response after partial hepatectomy, which peaks at 24 hr in rats. Indirect indexes of regeneration of the transplanted livers also were measured: plasma or serum ornithine decarboxylase; insulin and glucagon serum levels; estradiol and testosterone serum levels (and their nuclear and cytosolic receptors); and transforming growth factor-~, c-Ha-ras and c-jun mRNA expressions. With the small-for-size transplantation, these followed the same delayed pattern as the direct regeneration parameters. The small livers gradually increased in size over the course of 1 to 2 wk and achieved a volume equal to that of the liver originally present in the recipient. In contrast, no significant liver weight gain occurred in the transplanted livers from same-size donors despite the evidence of regeneration by direct indexes, but not by most of the surrogate parameters, including ornithine decarboxylase. (HEPATOLOGY 1993;19:210-216.) It has previously been demonstrated, both in human beings (1) and in dogs (2), that a liver from a small donor transplanted into a larger recipient undergoes hypertrophic and hyperplastic changes that result in a progressive increase of liver volume, until the trans-

Platelets in liver regeneration

“…The liver is the only organ that responds to a loss of functional tissue by a process of compensatory growth, also called ‘ regeneration’ , to reach a volume sufficient to meet the physiological requirements of the organism . Liver regeneration allows the liver to recover from toxic or viral injuries but also allows performance of partial hepatectomy and partial liver transplantation .…”

Severe Preservation Injury Induces Il-6/STAT3 Activation with Lack of Cell Cycle Progression After Partial Liver Graft Transplantation

“…Except in pediatric recipients, these grafts are typically significantly smaller than a calculated standard liver volume, with a minimal volume of liver mass necessary for successful recovery (1–3). Both animal studies and clinical experience have demonstrated decreased function and poor survival of grafts that do not make these minimal requirements, a condition termed ‘small‐for‐size’, manifested by prolonged cholestasis and appearance of significant ischemic‐type injury on pathologic review (4,5). However, the mechanisms of this type of injury, the reasons for graft failure and particularly the ability of the partial liver graft to regenerate after transplantation are not well defined.…”

Improving Research Practice in Rat Orthotopic and Partial Orthotopic Liver Transplantation: A Review, Recommendation, and Publication Guide

“…A reduced GRWR in rat OLT can be achieved by two methods: (1) using body weight (BW)-mismatched donor and recipient animals [49] or (2) via reducing the graft size by liver resection [37]. Zhong and colleagues [35,50,51,52] have repeatedly reported on the model of 25% small-for-size liver transplantation using BW-mismatched animals.…”

“…Besides transplantation models, numerous experimental approaches are known and used to investigate the phenomenon and mechanisms of transplantation injury [110], small-for-size syndrome [49,60], immunology/rejection [111], cold/warm ischemia-reperfusion [110,112,113], and regeneration of the liver [60,114]. …”