Endothelial progenitor cell transplantation improves the survival following liver injury in mice
Endothelial progenitor cell transplantation improves the survival following liver injury in mice
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DOI：
10.1053/j.gastro.2005.10.050
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发表时间：
2006-02-01
期刊：
影响因子：
29.4
通讯作者：
Sata, M
中科院分区：
文献类型：
--
作者：
Taniguchi, E;Kin, M;Sata, M
背景和目标：新血管形成对损伤组织的愈合至关重要，最近已经发现包括血管生成和血管发生，血管生成涉及成熟的内皮细胞，血管发生涉及内皮祖细胞。本研究的目的是阐明内皮祖细胞在出生后肝再生过程中的可能作用。研究方法：为了确定内皮祖细胞如何参与肝再生，将人或小鼠内皮祖细胞移植到四氯化碳诱导的急性肝损伤小鼠体内。计算内皮祖细胞移植组和对照组小鼠的存活率。分别对两组暂时切除的肝脏进行检查。结果如下：早期移植的人肝细胞前体细胞主要分布在肝中央静脉周围，肝细胞广泛坏死;后期移植细胞形成管状结构。沿肝窦沿着观察到更多的这些细胞。移植人或小鼠内皮祖细胞改善了肝损伤后小鼠的存活率（分别从28.6%至85.7%，P <0.0005和从33.3%至80.0%，P <0.001），同时伴有肝细胞的更大增殖。人血管内皮祖细胞产生几种生长因子，如肝细胞生长因子、转化生长因子-α、肝素结合表皮生长因子样生长因子和血管内皮生长因子，并且还引起内源性生长因子。结论：内皮祖细胞移植后，内源性和外源性生长因子和直接新生血管促进肝再生，从而提高肝损伤后的生存率。肝细胞移植是促进肝再生的一种新的治疗策略。
Background & Aims: Neovascularization, which is vital to the healing of injured tissues, recently has been found to include both angiogenesis, which involves in mature endothelial cells, and vasculogenesis, involving enclothelial progenitor cells. The aim of this study was to clarify the possible roles of enclothelial progenitor cells during postnatal liver regeneration. Methods: To determine how enclothelial progenitor cells participate in liver regeneration, human or mouse enclothelial progenitor cells were transplanted into the mice with carbon tetrachloride-induced acute liver injury. Survival rate of the mice in endothelial progenitor cell-transplanted and control groups was calculated. Separately, livers removed temporally from both groups were examined. Results: At an early stage, transplanted human enclothelial progenitor cells were seen mainly surrounding hepatic central veins where hepatocytes showed extensive necrosis; later, the transplanted cells formed tubular structures. More of these cells were observed along hepatic sinusoids. Transplantation of human or mouse endothelial progenitor cells improved survival of the mice following liver injury (from 28.6% to 85.7%, P < .0005 and from 33.3% to 80.0%, P < .001, respectively), accompanied by greater proliferation of hepatocytes. Human enclothelial progenitor cells produced several growth factors, such as hepatocyte growth factor, transforming growth factor-alpha, heparin-binding epidermal growth factor-like growth factor, and vascular endothelial growth factor, and also elicited endogenous growth factors. Conclusions: Endogenous and exogenous growth factors and direct neovascularization after endothelial progenitor cell transplantation promoted liver regeneration, thus improving survival after liver injury. Transplantation of enclothelial progenitor cells could represent a new therapeutic strategy for promoting liver regeneration.