在动物模型中，间充质基质细胞的局部应用改善了缺血再灌注损伤后的肝实质损伤。
Topical Application of Mesenchymal Stromal Cells Ameliorated Liver Parenchyma Damage After Ischemia-Reperfusion Injury in an Animal Model.
作者信息
Lam Ping Kuen, Chong Charing Ching Ning, Lo Anthony Wing Ip, Chan Anthony Wing Hung, Tong Cindy See Wai, Chin Don Wai Ching, Wong Kenneth Hoi Kin, Choy Richard Kwong Wai, Fung Andrew Kai-Yip, Wang Yi Xiang, To Ka Fai, Lai Paul Bo San
机构信息
Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Chow Tai Fook-Cheng Yu Tung Surgical Stem Cell Research Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
出版信息
Transplant Direct. 2017 May 11;3(6):e160. doi: 10.1097/TXD.0000000000000675. eCollection 2017 Jun.
BACKGROUND
Ischemia-reperfusion injury (IRI) is commonly encountered after liver surgery. This study evaluated the hepatoprotective effects of topically applied adipose-derived mesenchymal stromal cells (ADMSCs) on hepatic IRI in a rat model.
METHODS
ADMSCs from transgenic green fluorescent protein Sprague-Dawley rats were topically applied to the liver surface of Sprague-Dawley rats after hepatic IRI and fixed in position by fibrin glue (group A, n = 24). An equivalent amount of ADMSCs were administered through the portal (group B, n = 24) or tail vein (group C, n = 24). In the control group (group D, n = 20), no treatment was given to the IRI liver.
RESULTS
All the rats in group A and group D survived. Within 2 days after hepatic IRI, only 50% of rats survived in group B, and ADMSCs were detected in thromboemboli within large vessels. 62.5% of the rats died in group C because most of the ADMSCs were trapped in the lungs. ADMSCs migrated across the liver capsule and homed to the injured liver parenchyma 3 days after topical application in group A. The homed ADMSCs expressed hepatocyte nuclear factor-4α and hepatocyte nuclear factor-1. Compared with group D, the rate of hepatic regeneration in group A was enhanced with less inflammation, smaller necrotic areas, and improved liver function. Proinflammatory cytokines IL-6, IL-21, and CD70 were significantly downregulated in group A by 6.3-, 2.7-, and 12.7-fold, respectively ( < 0.05). The neurogenic locus NOTCH homolog protein pathway was activated in the topical ADMSCs.
CONCLUSIONS
Topically applied adipose-derived mesenchymal stromal cells demonstrated hepatoprotective effects on hepatic IRI in an animal model.
背景
缺血再灌注损伤（IRI）在肝脏手术后较为常见。本研究评估了局部应用脂肪间充质干细胞（ADMSCs）对大鼠肝脏IRI的肝保护作用。
方法
将来自转基因绿色荧光蛋白Sprague-Dawley大鼠的ADMSCs在肝脏IRI后局部应用于Sprague-Dawley大鼠的肝脏表面，并用纤维蛋白胶固定在位（A组，n = 24）。等量的ADMSCs通过门静脉（B组，n = 24）或尾静脉（C组，n = 24）给药。对照组（D组，n = 20）的IRI肝脏未接受任何治疗。
结果
A组和D组的所有大鼠均存活。肝脏IRI后2天内，B组仅有50%的大鼠存活，且在大血管内的血栓栓子中检测到ADMSCs。C组62.5%的大鼠死亡，因为大多数ADMSCs被困在肺部。A组局部应用后3天，ADMSCs穿过肝包膜迁移并归巢至受损的肝实质。归巢的ADMSCs表达肝细胞核因子-4α和肝细胞核因子-1。与D组相比，A组的肝再生率提高，炎症减轻，坏死面积减小，肝功能改善。A组中促炎细胞因子IL-6、IL-21和CD70分别显著下调6.3倍、2.7倍和12.7倍（<0.05）。局部ADMSCs中的神经源性Notch同源蛋白途径被激活。
结论
在动物模型中，局部应用脂肪间充质干细胞对肝脏IRI具有肝保护作用。
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