Establishment of Functional Liver Spheroids From Human Hepatocyte-Derived Liver Progenitor-Like Cells for Cell Therapy.
Establishment of Functional Liver Spheroids From Human Hepatocyte-Derived Liver Progenitor-Like Cells for Cell Therapy.
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从人肝细胞来源的肝祖样细胞建立功能性肝球体用于细胞治疗。
DOI：
10.3389/fbioe.2021.738081
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发表时间：
2021
影响因子：
5.7
通讯作者：
Yan HX
中科院分区：
文献类型：
--
作者：
Liu WM;Zhou X;Chen CY;Lv DD;Huang WJ;Peng Y;Wu HP;Chen Y;Tang D;Guo LN;Wang XL;Zhang HD;Liu XH;Yang LQ;Yu WF;Yan HX
在全球范围内，每年约有200万人死于肝病。肝移植是治疗严重终末期肝病的唯一可靠方法，然而，器官供体的短缺是一个巨大的限制。人肝细胞来源的肝祖细胞样细胞（HepLPCs）已被报道为开发体外模型、细胞疗法和组织工程应用的肝细胞的新来源，但其作为移植供体的功能尚不清楚。在这里，一个三维（3D）共培养系统，使用HepLPC和人脐静脉内皮细胞（HUVEC）的开发。这些HepLPC球体模仿成熟肝细胞的细胞相互作用和结构，通过超微结构形态，基因表达谱和功能测定证实。封装在藻酸盐珠中的HepLPC能够减轻用四氯化碳（CCL4）处理的小鼠的肝损伤，而藻酸盐涂层保护细胞免受免疫攻击。我们证实了这些现象是由于HUVECs产生胶质细胞源性神经营养因子（GDNF）促进HepLPCs成熟并通过MET磷酸化增强HepLPCs紧密连接。我们的研究结果显示海藻酸钠微囊化球体在急性肝损伤（ALF）动物模型中的有效性和安全性，这可能为细胞治疗提供新的策略。
Globally, about two million people die from liver diseases every year. Liver transplantation is the only reliable therapy for severe end-stage liver disease, however, the shortage of organ donors is a huge limitation. Human hepatocytes derived liver progenitor-like cells (HepLPCs) have been reported as a novel source of liver cells for development of in vitro models, cell therapies, and tissue-engineering applications, but their functionality as transplantation donors is unclear. Here, a 3-dimensional (3D) co-culture system using HepLPCs and human umbilical vein endothelial cells (HUVECs) was developed. These HepLPC spheroids mimicked the cellular interactions and architecture of mature hepatocytes, as confirmed through ultrastructure morphology, gene expression profile and functional assays. HepLPCs encapsulated in alginate beads are able to mitigate liver injury in mice treated with carbon tetrachloride (CCL4), while alginate coating protects the cells from immune attack. We confirmed these phenomena due to HUVECs producing glial cell line-derived neurotrophic factor (GDNF) to promote HepLPCs maturation and enhance HepLPCs tight junction through MET phosphorylation. Our results display the efficacy and safety of the alginate microencapsulated spheroids in animal model with acute liver injury (ALF), which may suggest a new strategy for cell therapy.
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3D 肝培养同时维持原代肝细胞和肝窦内皮细胞表型。
影响因子：
3.7
作者：
Kim Y;Rajagopalan P
通讯作者：
Rajagopalan P
人肝细胞来源的肝祖样细胞的扩增和分化及其在嗜肝病原体研究中的应用
影响因子：
44.1
作者：
Fu GB;Huang WJ;Zeng M;Zhou X;Wu HP;Liu CC;Wu H;Weng J;Zhang HD;Cai YC;Ashton C;Ding M;Tang D;Zhang BH;Gao Y;Yu WF;Zhai B;He ZY;Wang HY;Yan HX
通讯作者：
Yan HX
DOI：
10.1002/hep.29324
发表时间：
2017-11
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Kim DS;Ryu JW;Son MY;Oh JH;Chung KS;Lee S;Lee JJ;Ahn JH;Min JS;Ahn J;Kang HM;Kim J;Jung CR;Kim NS;Cho HS
通讯作者：
Cho HS
影响因子：
15.9
作者：
Hossain, Jubayer A.;Latif, Md A.;Miletic, Hrvoje
通讯作者：
Miletic, Hrvoje
影响因子：
64.5
作者：
Gao D;Vela I;Sboner A;Iaquinta PJ;Karthaus WR;Gopalan A;Dowling C;Wanjala JN;Undvall EA;Arora VK;Wongvipat J;Kossai M;Ramazanoglu S;Barboza LP;Di W;Cao Z;Zhang QF;Sirota I;Ran L;MacDonald TY;Beltran H;Mosquera JM;Touijer KA;Scardino PT;Laudone VP;Curtis KR;Rathkopf DE;Morris MJ;Danila DC;Slovin SF;Solomon SB;Eastham JA;Chi P;Carver B;Rubin MA;Scher HI;Clevers H;Sawyers CL;Chen Y
通讯作者：
Chen Y