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Decellularized human placenta supports hepatic tissue and allows rescue in acute liver failure
Hepatology ( IF 13.5 ) Pub Date : 2018-03-26 , DOI: 10.1002/hep.29713
Zurab Kakabadze 1 , Ann Kakabadze 1 , David Chakhunashvili 1 , Lia Karalashvili 1 , Ekaterine Berishvili 1 , Yogeshwar Sharma 2 , Sanjeev Gupta 2, 3, 4, 5, 6
Affiliation  

Tissue engineering with scaffolds to form transplantable organs is of wide interest. Decellularized tissues have been tested for this purpose, although supplies of healthy donor tissues, vascular recellularization for perfusion, and tissue homeostasis in engineered organs pose challenges. We hypothesized that decellularized human placenta will be suitable for tissue engineering. The universal availability and unique structures of placenta for accommodating tissue, including presence of embedded vessels, were major attractions. We found decellularized placental vessels were reendothelialized by adjacent native cells and bridged vessel defects in rats. In addition, implantation of liver fragments containing all cell types successfully hepatized placenta with maintenance of albumin and urea synthesis, as well as hepatobiliary transport of 99mTc‐mebrofenin, up to 3 days in vitro. After hepatized placenta containing autologous liver was transplanted into sheep, tissue units were well‐perfused and self‐assembled. Histological examination indicated transplanted tissue retained hepatic cord structures with characteristic hepatic organelles, such as gap junctions, and hepatic sinusoids lined by endothelial cells, Kupffer cells, and other cell types. Hepatocytes in this neo‐organ expressed albumin and contained glycogen. Moreover, transplantation of hepatized placenta containing autologous tissue rescued sheep in extended partial hepatectomy‐induced acute liver failure. This rescue concerned amelioration of injury and induction of regeneration in native liver. The grafted hepatized placenta was intact with healthy tissue that neither proliferated nor was otherwise altered. Conclusion: The unique anatomic structure and matrix of human placenta were effective for hepatic tissue engineering. This will advance applications ranging from biological studies, drug development, and toxicology to patient therapies. (Hepatology 2018;67:1956‐1969).

中文翻译:

脱细胞人胎盘支持肝组织并允许在急性肝衰竭中进行救援

用支架进行组织工程以形成可移植器官受到广泛关注。已为此目的测试了脱细胞组织,尽管健康供体组织的供应、用于灌注的血管再细胞化和工程器官中的组织稳态构成了挑战。我们假设脱细胞的人胎盘将适用于组织工程。胎盘用于容纳组织的普遍可用性和独特结构,包括嵌入血管的存在,是主要的吸引力。我们发现脱细胞胎盘血管被邻近的天然细胞再内皮化,并在大鼠中桥接血管缺陷。此外,植入包含所有细胞类型的肝脏碎片成功地使胎盘肝化,同时维持白蛋白和尿素的合成,以及 99mTc-mebrofenin 的肝胆转运,在体外长达 3 天。将含有自体肝脏的肝胎盘移植到绵羊体内后,组织单位得到良好的灌注和自组装。组织学检查表明移植的组织保留了具有特征性肝细胞器的肝索结构,如间隙连接和由内皮细胞、库普弗细胞和其他细胞类型排列的肝窦。这个新器官中的肝细胞表达白蛋白并含有糖原。此外,含有自体组织的肝胎盘移植挽救了延长部分肝切除术引起的急性肝衰竭的绵羊。这种拯救涉及天然肝脏损伤的改善和再生的诱导。移植的肝胎盘与健康组织完整无缺,既没有增殖也没有其他改变。结论:人胎盘独特的解剖结构和基质对肝组织工程是有效的。这将推动从生物学研究、药物开发和毒理学到患者治疗的应用。(肝病学 2018;67:1956-1969)。
更新日期:2018-03-26
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