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首页> 外文期刊>Tissue engineering, Part C. Methods >Expansion and hepatocytic differentiation of liver progenitor cells in vivo using a vascularized tissue engineering chamber in mice.
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Expansion and hepatocytic differentiation of liver progenitor cells in vivo using a vascularized tissue engineering chamber in mice.

机译：在小鼠体内使用血管化组织工程室在体内扩增肝祖细胞并进行肝细胞分化。

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Current cell-based treatment alternatives to organ transplantation for liver failure remain unsatisfactory. Hepatocytes have a strong tendency to dedifferentiate and apoptose when isolated and maintained in culture. In contrast, liver progenitor cells (LPCs) are robust, easy to culture and have been shown to replace damaged hepatocytes in liver disease. In this study we investigate whether isolated LPCs can survive and differentiate toward mature hepatocytes in vivo when implanted into a heterotopic mouse tissue engineering chamber model. Healthy Balb/c mice and those put on a choline-deficient ethionin-supplemented diet to induce chronic liver disease were implanted with a tissue engineering chamber based on the epigastric flow through pedicle model, containing either 1 x 10(6) LPCs suspended in Matrigel, or LPC-spheroids produced by preculture for 1 week in Matrigel. Four weeks after implantation the chamber contents were harvested. In all four groups, progenitor cells persisted in large numbers to 4 weeks and demonstrated evidence of considerable proliferation judged by Ki67-positive cells. Periodic acid Schiff staining demonstrated differentiation of some cells into mature hepatocytes. Constructs grown from LPC-spheroids demonstrated considerably greater LPC survival than those from LPCs that were grown as monolayers and implanted as dissociated cells. The combined use of LPC spheroids and the vascularized chamber model could be the basis for a viable alternative to current treatments for chronic liver failure.
机译：对于肝衰竭，当前基于细胞的器官移植替代疗法仍然不能令人满意。当分离并维持在培养物中时，肝细胞具有强烈的去分化和凋亡倾向。相比之下，肝祖细胞（LPC）健壮，易于培养，并已被证明可以替代肝病中受损的肝细胞。在这项研究中，我们调查了分离的LPCs植入异位小鼠组织工程室模型后是否能在体内存活并向成熟的肝细胞分化。将健康的Balb / c小鼠和补充了胆碱缺乏的乙硫蛋白的饮食诱导慢性肝病的小鼠植入组织工程腔室，该腔室基于通过蒂模型的上腹部流量，其中包含1 x 10（6）LPC悬浮在Matrigel中或在Matrigel中预培养1周产生的LPC球体。植入后四周，收集室内容物。在所有四个组中，祖细胞大量持续存在至4周，并显示出Ki67阳性细胞判断出的大量增殖证据。高碘酸希夫（Schiff）染色表明某些细胞分化为成熟的肝细胞。从LPC椭球体生长的构建体比从以单层形式生长并作为离体细胞植入的LPC的构建体显示出更高的LPC存活率。 LPC球体和血管化腔室模型的组合使用可能是当前治疗慢性肝衰竭的可行替代方法的基础。

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