骨髓间充质干细胞移植在大鼠急性肝损伤组织中的定植能力

背景：目前对于移植后的骨髓间充质干细胞在肝组织中的分化途径以及能够在多大程度上修复损伤的肝细胞等问题，尚未达成统一共识。 目的：观察经尾静脉移植的骨髓间充质干细胞在急性肝损伤大鼠肝组织中的定植分化情况。 设计、时间及地点：细胞学体内对照观察，于2007-12/2008-06在兰州大学中心实验室地点完成。 材料：清洁级6~8周龄雄性SD大鼠47只，取5只用于制备骨髓间充质干细胞，剩余42只随机分为3组：肝正常细胞移植组15只、肝损伤细胞移植组14只、肝损伤盐水对照组13只。 方法：肝损伤细胞移植组、肝损伤盐水对照组大鼠通过腹腔注射D-氨基半乳糖建立急性肝损伤模型。造模后24 h，肝损伤细胞移植组、肝正常细胞移植组经尾静脉注入BrdU标记的第3代大鼠骨髓间充质干细胞悬液1 mL，含(1.5~2.0)×106个细胞；肝损伤盐水对照组大鼠同法注入等量生理盐水。 主要观察指标：移植后肝功能恢复情况，肝脏免疫组织化学检测结果。 结果：与造模后24 h比较，移植后2，3周肝正常细胞移植组、肝损伤盐水对照组血清谷丙转氨酶活性无明显变化（P > 0.05）；肝损伤细胞移植组血清谷丙转氨酶活性明显降低(P < 0.05)，肝功能恢复较好。与肝正常细胞移植组比较，肝损伤细胞移植组Brdu+细胞数明显增多(P < 0.01)，多分布在汇管区及中央静脉周围，但随着时间延长BrdU+细胞数逐渐减少。 结论：经尾静脉移植的骨髓间充质干细胞可促进急性肝损伤大鼠的肝功能恢复，并能够在受损肝脏及正常肝脏中定植分化，且定植与分化的程度可能与肝脏损伤程度有关。

Homing ability of bone marrow mesenchymal stem cell transplantation in acute hepatic injury rats

BACKGROUND: There is no unified consensus in studies concerning differentiation of bone marrow mesenchymal stem cells (BMSCs) following transplantation and what is the degree of BMSCs transplantation in repair of hepatocytes. OBJECTIVE: To observe homing and differentiation of BMSCs via caudal vein transplantation in acute hepatic injury rats. DESIGN, TIME AND SETTING: The cytological in vivo study was performed at the Central Laboratory of Lanzhou University from December 2007 to June 2008. MATERIALS: A total of 47 clean male Sprague Dawley rats aged 6-8 weeks were used. Five rats were utilized for BMSCs preparation. The remaining 42 rats were randomly assigned into normal liver BMSCs group (n=15), injured liver BMSCs group (n=14), and injured liver saline group (n=13). METHODS: Rat models of acute hepatic injury were established by intraperitoneal injection of D-aminogalactose in the injured liver BMSCs group and injured liver saline group. 24 hours following model induction, 1 mL the third passage of BMSCs suspension containing (1.5-2.0)×106 cells labeled with BrdU was injected into rats in the injured liver BMSCs group and normal liver BMSCs group via the caudal vein. Rats in the injured liver saline group were infused with an equal volume of saline. MAIN OUTCOME MEASURES: Hepatic functional recovery following transplantation, and results of immunohistochemistry in the liver were measured. RESULTS: Compared with that at 24 hours following model induction, there were no significant changes in serum glutamate pyruvate transaminase activity in the normal liver BMSCs group and injured liver saline group at 2 and 3 weeks following transplantation (P > 0.05). Serum glutamate pyruvate transaminase activity significantly decreased in the injured liver BMSCs group (P < 0.05), and hepatic function recovered well. Compared with the normal liver BMSCs group, number of Brdu+ cells significantly increased in the injured liver BMSCs group (P < 0.01), and mostly distributed in the portal region and surrounding the central veins. With time prolonged, the number of Brdu+ cells gradually reduced. CONCLUSION: BMSCs transplanted through tail vein can promote the recovery of hepatic function in the acute hepatic injury rats, and can differentiate in the injured and normal livers. The homing and differentiation may be associated with the degree of liver injury.