Transplantation of basic fibroblast growth factor-pretreated adipose tissue-derived stromal cells enhances regression of liver fibrosis in mice
Transplantation of basic fibroblast growth factor-pretreated adipose tissue-derived stromal cells enhances regression of liver fibrosis in mice
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DOI：
10.1152/ajpgi.90463.2008
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发表时间：
2009-02-01
影响因子：
4.5
通讯作者：
Hayashi, Norio
中科院分区：
文献类型：
--
作者：
Kamada, Yoshihiro;Yoshida, Yuichi;Hayashi, Norio
[10]李文，李文.经碱性成纤维细胞生长因子预处理的脂肪基质细胞移植促进小鼠肝纤维化的消退。美国生理学杂志胃肠和肝脏生理学296：G157-G167，2009。首次发表于2008年12月4日; doi：10.1152/ajpgi.90463.2008。脂肪组织来源的基质细胞（ADSC）有可能分化为与骨髓来源的间充质基质细胞（BMSC）相似的各种细胞类型。与BMSC不同，ADSC可以容易地和重复地收获。然而，ADSC用于肝病细胞移植的优势仍不清楚。为了研究这一点，我们开发了一种新的ADSC培养系统，以及ADSC移植到小鼠肝脏中的有效方法。从雄性C57 BL 6/J小鼠的皮下脂肪组织中分离ADSC，并在有或无碱性成纤维细胞生长因子（bFGF）的塑料培养皿中培养。在体内研究中，将从绿色荧光蛋白转基因小鼠中分离的ADSC移植到四氯化碳损伤的C57 BL 6/J小鼠肝脏中。bFGF处理的ADSC表达了几种肝脏特异性标记基因，并表现出与肝脏相关的功能，如白蛋白分泌、糖原合成、尿素产生和低密度脂蛋白摄取。更重要的是，用bFGF预处理ADSC 1周可提高ADSC在小鼠肝脏中的再增殖率，减轻肝纤维化，并恢复正常的血清丙氨酸氨基转移酶和白蛋白水平。结果表明，碱性FGF促进ADSC在体外转分化为肝系细胞，bFGF预处理的ADSC移植减少小鼠肝纤维化。ADSC是一种潜在的有价值的移植治疗细胞来源。
Kamada Y, Yoshida Y, Saji Y, Fukushima J, Tamura S, Kiso S, Hayashi N. Transplantation of basic fibroblast growth factor-pretreated adipose tissue-derived stromal cells enhances regression of liver fibrosis in mice. Am J Physiol Gastrointest Liver Physiol 296: G157-G167, 2009. First published December 4, 2008; doi:10.1152/ajpgi.90463.2008.-Adipose tissue-derived stromal cells (ADSC) potentially differentiate into various cell types similar to bone marrow-derived mesenchymal stromal cells (BMSC). Unlike BMSC, ADSC can be harvested easily and repeatedly. However, the advantages of ADSC for cell transplantation in liver disease remain unclear. To investigate this, we developed a novel culture system for ADSC, as well as effective methods for transplantation of ADSC into mice liver. ADSC were isolated from subcutaneous adipose tissues of male C57BL6/J mice and cultured on plastic dishes with or without basic fibroblast growth factor (bFGF). In the in vivo study, ADSC isolated from green fluorescent protein-transgenic mice were transplanted into carbon tetrachloride-injured C57BL6/J mice liver. bFGF-treated ADSC expressed several liver-specific marker genes and demonstrated liver-related functions such as albumin secretion, glycogen synthesis, urea production, and low-density lipoprotein uptake. Importantly, pretreatment of ADSC with bFGF for 1 wk enhanced the repopulation rate of ADSC in mice liver, attenuated liver fibrosis, and restored normal serum alanine aminotransferase and albumin levels. The results indicate that basic FGF facilitates transdifferentiation of ADSC into hepatic lineage cells in vitro and that transplantation of bFGF-pretreated ADSC reduced hepatic fibrosis in mice. ADSC are a potentially valuable source of cells for transplantation therapy.