Zhao Wen-Li, Chen Yao-Kai, Zhang Rong, Wang Yu-Ming
Department of Infectious Diseases, The Third Military Medical University, Chongqing 400038, China.
Sheng Wu Gong Cheng Xue Bao. 2007 May;23(3):467-70.
To repopulate the liver of mice with acute liver injury and to make mouse models with chimeric liver by using human umbilical cord blood (hUCB)-derived mononuclear cells.
Fifteen acute liver injury mouse models were induced by carbon tetrachloride intraperitoneal injection followed by two-thirds hepatectomy and all mice were divided into three groups: cell transplantation group (n = 7), negative control group (n = 3) and blank control group (n = 5). HUCB cell preparations were transplanted into mouse spleens of cell transplantation group and phosphate bufferd saline (PBS) was injected into spleens of negative controls. Neither cell suspension nor PBS was given to the blank controls. Pathological changes were observed 7, 14 and 21 days after cell transplantation. Human albumin (ALB) and cytokeratin 19 (CK19) were also detected in the mouse sera and liver tissues.
All mice showed histological features of acute liver injury. Positive expression of human ALB and CK19 were observed in liver tissues of cell transplantation group 7, 14 and 21 days after cell transplantation. Human ALB could be detected from the sera and liver homogenates of cell-transplanted mice. No positive expression of human ALB and CK19 were observed in liver tissues and no human ALB was detected in sera of negative control group.
HUCB-derived mononuclear cells can differentiate into functional human hepatocytes and biliary cells in large quantity in mouse models with acute liver injury, thus a great progress were made in establishing mouse models with chimeric liver.
利用人脐带血(hUCB)来源的单核细胞使急性肝损伤小鼠的肝脏重新细胞化,并制作嵌合肝小鼠模型。
通过腹腔注射四氯化碳诱导15只急性肝损伤小鼠模型,随后进行三分之二肝切除术,将所有小鼠分为三组:细胞移植组(n = 7)、阴性对照组(n = 3)和空白对照组(n = 5)。将hUCB细胞制剂移植到细胞移植组小鼠的脾脏中,将磷酸盐缓冲盐水(PBS)注射到阴性对照组小鼠的脾脏中。空白对照组既不给予细胞悬液也不给予PBS。在细胞移植后7、14和21天观察病理变化。还检测了小鼠血清和肝组织中的人白蛋白(ALB)和细胞角蛋白19(CK19)。
所有小鼠均表现出急性肝损伤的组织学特征。在细胞移植组细胞移植后7、14和21天,肝组织中观察到人类ALB和CK19的阳性表达。在细胞移植小鼠的血清和肝匀浆中可检测到人类ALB。阴性对照组肝组织中未观察到人类ALB和CK19的阳性表达,血清中未检测到人类ALB。
在急性肝损伤小鼠模型中,hUCB来源的单核细胞可大量分化为功能性人肝细胞和胆管细胞,从而在建立嵌合肝小鼠模型方面取得了重大进展。