Liver Cold Storage and Transplantation in the Cold-Adaptive Daurian Ground Squirrels

Zipei Wang; Haobin Sun; Xin Xing; Yuqing Qiao; Xiaoling Ren; Jingxing Ou; Zhishui Chen; Bo Yang

doi:10.3791/68444

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Method Article

Liver Cold Storage and Transplantation in the Cold-Adaptive Daurian Ground Squirrels

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DOI:

10.3791/68444

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July 3rd, 2025

Zipei Wang^*¹^,²^,³^,⁴^,⁵ , Haobin Sun^*⁶^,⁷^,⁸ , Xin Xing^*⁹ , Yuqing Qiao⁹ , Xiaoling Ren⁶^,⁷ , Jingxing Ou⁶^,⁷^,⁸ , Zhishui Chen¹^,²^,³^,⁴^,⁵ , Bo Yang¹^,²^,³^,⁴^,⁵

¹Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, ²Key Laboratory of Organ Transplantation, Ministry of Education, ³NHC Key Laboratory of Organ Transplantation, ⁴Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, ⁵Organ Transplantation Clinical Medical Research Center of Hubei Province, ⁶Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University, ⁷Guangdong Province engineering laboratory for transplantation medicine, Organ Transplantation Research Center of Guangdong Province, ⁸Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, ⁹College of Life Science, Shenyang Normal University

^* These authors contributed equally

Summary

Here, we present a protocol to establish a long-term liver cold storage and transplantation model in Daurian ground squirrel (DGS), which has been technically challenging in standard rodent models.

Abstract

In liver transplantation, the functional recovery of donor grafts following extended cold storage is a major challenge. The same obstacle applies to standard rodent models (e.g., mice and rats) for liver transplantation despite their well-established surgical protocols, thus restricting research on key topics such as post-transplantation functional recovery and host-graft immunocompatibility. Here, we successfully established a novel liver transplantation model using an obligate hibernator, the Daurian ground squirrel (DGS; Spermophilus dauricus), which demonstrates intrinsic adaptation to ultra profound hypothermia-rewarming and ischemia-reperfusion transitions. In our hands, transplantation of liver grafts following 24-h cold storage resulted in 100% survival of DGS recipients within the 7-day observation time frame, whilst the same procedure in Sprague-Dawley (SD) rats had 0% survival 24 h following the surgery. Thus, the DGS and other cold-adaptive mammalian models provide a unique and robust platform to investigate mechanisms underlying organ cold adaptation and transplantation tolerance, which can support the development of novel treatment or surgery strategies in the field of transplantation medicine.

Introduction

Cold-rewarming and ischemia-reperfusion are significant contributors to liver graft injury, increasing the risk of early allograft dysfunction. Although liver transplantation in standard rodent organisms such as mice and rats has been successfully established¹^,², because studies on these cold-intolerant species provide limited insights into the mechanisms of cold adaptation, advancements in organ preservation and transplantation medicine have been hindered.

Developing transplantation research models in suitable cold-adaptive species may fill such a gap. For example, mammalian hibern....