公开(公告)号：US20100143313A1

公开(公告)日：2010-06-10

申请号：US12634983

申请日：2009-12-10

申请人： Martin L. Yarmush ,  Cheul H. Cho ,  Arno W. Tilles

发明人： Martin L. Yarmush ,  Cheul H. Cho ,  Arno W. Tilles

IPC分类号： A61K35/407 ,  C12N5/074 ,  A61P1/16

CPC分类号： A61K35/407 ,  C12N5/067 ,  C12N2500/30 ,  C12N2500/62 ,  C12N2501/23 ,  C12N2501/385 ,  C12N2501/39 ,  C12N2502/14 ,  C12N2506/02

摘要： One of the major hurdles of cellular therapies for the treatment of liver failure is the low availability of functional human hepatocytes. Although embryonic stem (ES) cells represent a potential cell source for therapy, current methods for differentiation result in mixed cell populations or low yields of the cells of interest. The present invention provides for a rapid, direct differentiation method that yields a homogeneous population of endoderm-like cells with 95% purity. In one embodiment, mouse ES cells cultured on top of collagen-sandwiched hepatocytes differentiate and proliferate into a uniform and homogeneous cell population of endoderm-like cells. The endoderm-like cell population was positive for Foxa2, Sox17 and AFP, and could further differentiate into hepatocyte-like cells that demonstrate hepatic morphology, functionality, and gene and protein expression. Incorporating the hepatocyte-like cells into a bioartificial liver device to treat fulminant hepatic failure improved animal survival, thereby underscoring the therapeutic potential of these cells.

摘要翻译： 用于治疗肝衰竭的细胞疗法的主要障碍之一是功能性人肝细胞的可用性低。 尽管胚胎干细胞（ES）细胞代表治疗的潜在细胞来源，但目前的分化方法导致混合细胞群体或感兴趣细胞的低产量。 本发明提供快速，直接的分化方法，其产生具有95％纯度的内胚层样细胞的均匀群体。 在一个实施方案中，在胶原夹心的肝细胞上培养的小鼠ES细胞分化并增殖成内胚层样细胞的均匀且均匀的细胞群。 内皮样细胞群对Foxa2，Sox17和AFP呈阳性，可进一步分化为肝细胞样细胞，其表现出肝脏形态，功能，基因和蛋白质表达。 将肝细胞样细胞结合到生物人工肝脏装置中以治疗暴发性肝衰竭改善了动物存活，从而强调了这些细胞的治疗潜力。

公开(公告)号：US20190134263A1

公开(公告)日：2019-05-09

申请号：US14003062

申请日：2012-03-01

申请人： Cheul H Cho ,  Ali Hussain ,  George Collins ,  Divya Ranendran

发明人： Cheul H Cho ,  Ali Hussain ,  George Collins ,  Divya Ranendran

IPC分类号： A61L27/26

摘要： The present invention relates to a vascularized three dimensional construct for thick tissue, a process for making the construct and to the use of the construct in tissue regeneration and repair and in drug development. The three-dimensional (3-D) tissue technology is used to generate vascularized, biomimetic tissue models in vitro utilizing a biodegradable nanofiber scaffold. The culture system allows the maintenance of long-term survival and function of liver and heart cells. The system utilizes a novel approach to generate structures that mimic in vivo tissue architecture. The system provides a microenvironment for forming 3-D microvascular networks within the nanofiber scaffolds.