Adipose-derived stem cell-based treatment for acute liver failure.
Adipose-derived stem cell-based treatment for acute liver failure.
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DOI：
10.1186/s13287-015-0040-2
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发表时间：
2015-03-21
影响因子：
7.5
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Chen G;Jin Y;Shi X;Qiu Y;Zhang Y;Cheng M;Wang X;Chen C;Wu Y;Jiang F;Li L;Zhou H;Fu Q;Liu X
急性肝衰竭（ALF）是一种高度致命的疾病，有效的治疗方法有限。虽然同种异体肝移植是治疗ALF的可行方法，但肝脏供体严重短缺。最近的研究表明，干细胞移植是一种更有希望的替代方法。因此，我们在大鼠模型研究的基础上，探讨了人脂肪源性干细胞（ASCs）是否具有治疗ALF的潜力。采用d -半乳糖胺注射建立大鼠ALF模型。这些大鼠被随机分为人类asc治疗组和磷酸盐缓冲盐水（PBS）对照组。将人ASCs或PBS经大鼠脾脏移植。动态检测肝功能、肝脏组织学指标，统计大鼠存活率。采用双荧光免疫组化检测移植后ASC的命运。此外，将浓缩的ASC条件培养基和ASC裂解液经大鼠股骨血管移植，研究其对ALF的治疗潜力。与假对照组相比，ASC移植组的生存能力有所提高。组织学和生化分析表明，在细胞增殖和凋亡方面，肝脏形态和功能得到改善。尽管过多的ASCs持续存在于脾脏，但肝功能的改善是明显的。然而，ASCs在移植到肝脏后3天内没有分化成肝细胞。此外，浓缩无血清ASC条件培养基和高水平肝细胞生长因子和血管内皮生长因子的ASC裂解物在提高ALF大鼠存活率方面均有明显改善。我们的数据表明，ASC移植具有治疗ALF的潜力，部分原因是其分泌生长因子促进肝脏再生的机制。
Acute liver failure (ALF) is a highly lethal disease, for which effective therapeutic methods are limited. Although allogeneic liver transplantation is a viable treatment method for ALF, there is a serious shortage of liver donors. Recent studies suggest that stem cell transplantation is a more promising alternative. Hence, we investigate whether human adipose-derived stem cells (ASCs) have the therapeutic potential for ALF in this study based on the studies of rat models. Sprague Dawley rats were used to establish ALF models by D-galactosamine injection. These rats were randomly divided into a human ASC-treated group and a phosphate-buffered saline (PBS) control group. The human ASCs or PBS was transplanted through the spleen of rats. The indices of hepatic function and hepatic histology were dynamically detected, and the survival rates of rats were also counted. Double-fluorescence immunohistochemistry was employed to detect the ASC fate after transplantation. Moreover, both concentrated ASC conditional media and ASC lysates were transplanted through the femoral vain of rats to investigate the therapeutic potential for ALF. The ASC transplantation group showed improved viability in comparison with the sham control. Histological and biochemical analysis suggested that liver morphology and function were improved in terms of cell proliferation and apoptosis. Although a plethora of ASCs persist in the spleen, the improvement in liver function was obvious. However, ASCs did not differentiate into hepatocytes after engrafting to livers within 3 days. In addition, both concentrated serum-free ASC conditional media and ASC lysates, characterized by high levels of hepatocyte growth factor and vascular endothelial growth factor, demonstrated obvious improvement in terms of high survival rates of ALF rats. Our data suggest that ASC transplantation has the potential for ALF treatment partly by the mechanism of secreting growth factors contributing to liver regeneration.
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影响因子：
5.1
作者：
Meier, M;Woywodt, A;Strassburg, CP
通讯作者：
Strassburg, CP
影响因子：
3.6
作者：
KEPPLER, D;LESCH, R;DECKER, K
通讯作者：
DECKER, K
影响因子：
5.2
作者：
Kern, Susanne;Eichler, Hermann;Bieback, Karen
通讯作者：
Bieback, Karen
影响因子：
13.5
作者：
Herrera, Maria Beatriz;Fonsato, Valentina;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
影响因子：
10.9
作者：
Cawthorn, William P.;Scheller, Erica L.;MacDougald, Ormond A.
通讯作者：
MacDougald, Ormond A.