Establishment of an Acute Graft-Versus-Host Disease Model Following Liver Transplantation in Donor-Dominant One-Way Major Histocompatibility Complex Matching Rats

Chen, W.; Wang, X.G.; Liu, Liang; Bai, Xueli; Wang, L.Y.; Wang, H.P.; Liang, Tingbo

doi:10.1016/j.transproceed.2008.11.008

Cited by 10 publications

(17 citation statements)

References 49 publications

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“…In addition, no significant differences in the serum ALT or AST levels after LT were observed between the 3 groups (Fig. 2R,S), and their liver function was normal; these findings were consistent with our previous work 19…”

Section: Resultssupporting

confidence: 92%

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Mesenchymal stem cells administered after liver transplantation prevent acute graft-versus-host disease in rats

Xia

Chen

et al. 2012

Liver Transpl

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Acute graft-versus-host disease is a serious and life-threatening complication of liver transplantation (LT) that occurs in 1% to 2% of liver allograft recipients. It is associated with a high mortality rate, and effective therapies are lacking. In our established rat model, a relative decrease in regulatory T cells (Tregs) was previously shown to be associated with acute graft-versus-host disease after liver transplantation (LT-aGVHD). Mesenchymal stem cells (MSCs) have been used to treat graft-versus-host disease after allogeneic hematopoietic stem cell transplantation, and they have been shown to induce Tregs, which have immunomodulatory effects. In this study, when a treatment with donor-or recipient-derived MSCs was administered from day 8 to day 14 after the typical symptoms of LT-aGVHD started, the recipients were not cured, and their survival time was not prolonged. However, when MSCs of different origins were administered from day 0 to day 6 after LT, the recipients survived significantly longer than the control group, and the surviving MSC-treated rats did not show typical LT-aGVHD symptoms. In vivo tracings of carboxyfluorescein diacetate succinimidyl ester-stained MSCs did not show significant accumulations in the target organs after administration. Flow cytometry analysis showed that the Treg ratios in peripheral blood were more higher for the MSC-treated groups versus the control group. More immunohistochemically stained forkhead box P3-positive cells were also found in the intestines of the MSC-treated groups versus the control group. Further investigations of the function of MSCs showed that they could increase the Treg ratio in a mixed lymphocyte reaction (MLR) and lead to a greater reduction in MLR proliferation in vitro. In conclusion, the post-LT administration of MSCs of either donor or recipient origin could prevent the onset of LT-aGVHD in our rat model. Liver Transpl 18:696-706, 2012. V C 2012 AASLD.

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Section: Resultssupporting

confidence: 92%

“…In this study, a rat model of LT-aGVHD that we previously established 19 was used to determine whether MSCs exhibit the same immune inhibitory effects in LT-aGVHD that they exhibit in BMT-aGVHD. This could provide evidence for a novel approach to the prevention or treatment of clinical LT-aGVHD.…”

mentioning

confidence: 99%

Mesenchymal stem cells administered after liver transplantation prevent acute graft-versus-host disease in rats

Xia

Chen

et al. 2012

Liver Transpl

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“…In our previous study, the reproducible rat model of LTx-aGVHD has been established for the first time by performing LT from Lewis to (LewisXBN)F1 rat in combination with donor splenocyte transfusion [23]. And after the transfusion of 4 × 10 8 donor splenocytes, simultaneous with liver transplantation, all recipients developed lethal aGVHD.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we investigate the level of chimerism in the peripheral blood that indicates the abnormal engraftment of donor lymphocytes in our previously established rat model with acute graft-versus-host disease following liver transplantation [23, 24] and found that this is an effective and senitive method in the early diagnosis of LTx-aGVHD.…”

Section: Introductionmentioning

confidence: 99%

Correlation of Chimerism with Acute Graft-versus-Host Disease in Rats following Liver Transplantation

Chen

Bai

et al. 2011

International Journal of Hepatology

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The accurate diagnosis of acute graft-versus-host disease following liver transplantation (LTx-aGVHD) has been hampered. Chimerism appears in the majority of recipients after LT and its significance in the diagnosis of LTx-aGVHD has not been clearly established. To demonstrate the significance of chimerism on the diagnosis of LTx-aGVHD, we compared the change of chimerism in syngeneic LT recipients, semiallogeneic LT recipients, and LTx-aGVHD induced recipients. Chimerism in PBMCs following sex-mismatched LT was identified by real-time PCR based on a rat Y-chromosome-specific primer. All recipients in semiallogeneic group grew in a normal pattern. However, when 4 × 108 donor splenocytes were transferred simultaneously during LT, the morbidity of lethal aGVHD was 100%. The chimerism appeared slightly higher in the semiallogeneic group than in the syngeneic LT group, but the difference was not significant. However, when the recipients developed lethal aGVHD after LT, chimerism in the PBMCs increased progressively, and even at an early time, a significant increase in chimerism was observed. In conclusion, high level chimerism correlated well with LTx-aGVHD, and detection of chimerism soon after transplantation may be of value in the diagnosis of LTx-aGVHD prior to the onset of symptoms.

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“…The suprahepatic IVC was reconstructed using continuous 7-0 polypropylene sutures. Furthermore, the portal vein and infrahepatic IVC were anastomosed using the two-cuff method modified from that described previously [6][7][8][9]. The graft was reperfused before anastomosing with the infrahepatic IVC.…”

Section: Methodsmentioning

confidence: 99%

A better way to do small-for-size liver transplantation in rats

et al. 2011

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Establishing a model for small-for-size liver transplantation is the basis for this study of partial and living donor graft liver transplantation. This study aims to explore a simpler and more effective way of establishing a 30% small-for-size liver transplantation in rats. Sprague-Dawley rats were selected as the donors and recipients. Small-for-size orthotopic liver transplantation was performed using Kamada's two-cuff method. The donor's liver was flushed via the abdominal aorta and hepatectomy was performed in situ. The animals were divided into three groups depending on the graft selected, with 40 pairs of rats in each group. In group I, the median lobe of the liver was used as graft; in group II, the right half of the median lobe and the right lobe were used as graft; and in group III, the median and right lobes were used as graft. In groups I and II, the bodyweights of donors were the same as those of recipients; however, in group III the bodyweights of donors were 100-120 g less than those of the recipients. The duration needed for transplantation, the 7-day survival rates, and the technical complication rates were compared among these three groups. The time required for hepatectomy was shorter in group III compared with groups I and II (8.8±0.7 min vs. 11.5±1.1 min and 10.1±1.0 min, P = 0.001). The cold ischemia time for the grafts, the anhepatic times, and the transplantation times for the recipients were not significantly different among the three groups. Compared with groups I and II, the incidence of bleeding, bile leakage, and inferior vena caval strictures were significantly decreased in group III (P<0.05). No significant differences between the three groups were found based on other complications after the operation (P>0.05). Group III had better 7-day survival rates and longer median survival times but the differences were not statistically significant. The method of small for donor bodyweight using the median and right lobes for grafting may be a more effective and simpler way of establishing a 30% small-for-size liver transplantation in rats, as shown by the shorter hepatectomy time and the occurrence of fewer complications after the operation.

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Establishment of an Acute Graft-Versus-Host Disease Model Following Liver Transplantation in Donor-Dominant One-Way Major Histocompatibility Complex Matching Rats

Cited by 10 publications

References 49 publications

Mesenchymal stem cells administered after liver transplantation prevent acute graft-versus-host disease in rats

Mesenchymal stem cells administered after liver transplantation prevent acute graft-versus-host disease in rats

Correlation of Chimerism with Acute Graft-versus-Host Disease in Rats following Liver Transplantation

A better way to do small-for-size liver transplantation in rats

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