Hong Jingxin, Jin Huajun, Han Junling, Hu Huanzhang, Liu Jian, Li Linfang, Huang Yao, Wang Dandan, Wu Mengchao, Qiu Lugui, Qian Qijun
Union Stem Cell and Gene Engineering Co., Ltd., Tianjin Cord Blood Bank, Tianjin 300384, P.R. China.
Laboratory of Viral and Gene Therapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China.
Mol Med Rep. 2014 Apr;9(4):1103-11. doi: 10.3892/mmr.2014.1927. Epub 2014 Jan 30.
Cirrhosis is the long‑term outcome of chronic hepatic injury and no effective therapy is currently available for this disease. Mesenchymal stromal cells (MSCs) are multipotent cells that are easily acquired and amplified, and may be potential candidates for cell therapy against cirrhosis. This study aimed to determine the therapeutic effects of human umbilical cord‑derived MSCs (hUCMSCs) for the treatment of liver cirrhosis and identify an effective method for engrafting MSCs. The model of liver cirrhosis was established by induction of diethylnitrosamine (DEN) in rats. The isolated hUCMSCs were identified by morphology, flow cytometry and multilineage differentiation; they were injected into the vein of DEN‑induced rats at varied cell doses and infusion times. Biochemical analyses of the serum and histopathological analysis of the liver tissues were performed to evaluate the therapeutic effects of hUCMSCs in all treatment groups. The results indicated that isolated hUCMSCs were capable of self‑replication and differentiated into multiple lineages, including osteoblast‑, adipocyte‑ and hepatocyte‑like cells. Compared with the control group, administration of hUCMSCs at different cell doses and infusion times relieved DEN‑induced cirrhosis to varying degrees. The therapeutic effects of hUCMSCs on liver cirrhosis gradually improved with increased cell dose and infusion times. The improvement of cirrhosis was due to the capacity of hUCMSCs to breakdown collagen fibers in the liver. It was demonstrated that infusion of hUCMSCs effectively relieved liver cirrhosis by facilitating the breakdown of collagen fibers in a dose‑dependent manner and multiple infusions caused a relatively greater improvement in cirrhosis compared with a single infusion of hUCMSCs.
肝硬化是慢性肝损伤的长期后果，目前尚无针对该疾病的有效治疗方法。间充质基质细胞（MSCs）是多能细胞，易于获取和扩增，可能是抗肝硬化细胞治疗的潜在候选者。本研究旨在确定人脐带间充质干细胞（hUCMSCs）对肝硬化的治疗效果，并确定一种有效的MSCs移植方法。通过在大鼠中诱导二乙基亚硝胺（DEN）建立肝硬化模型。通过形态学、流式细胞术和多谱系分化鉴定分离的hUCMSCs；将它们以不同的细胞剂量和输注时间注入DEN诱导的大鼠静脉中。对血清进行生化分析并对肝组织进行组织病理学分析，以评估所有治疗组中hUCMSCs的治疗效果。结果表明，分离的hUCMSCs能够自我复制并分化为多种谱系，包括成骨细胞、脂肪细胞和肝细胞样细胞。与对照组相比，在不同细胞剂量和输注时间给予hUCMSCs可不同程度缓解DEN诱导的肝硬化。hUCMSCs对肝硬化的治疗效果随着细胞剂量和输注时间的增加而逐渐改善。肝硬化的改善归因于hUCMSCs分解肝脏中胶原纤维的能力。结果表明，输注hUCMSCs通过以剂量依赖性方式促进胶原纤维的分解有效缓解肝硬化，与单次输注hUCMSCs相比，多次输注对肝硬化的改善相对更大。
