Development of liver microtissues with functional biliary ductular network.
Development of liver microtissues with functional biliary ductular network.
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DOI：
10.1002/bit.27546
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发表时间：
2021-01
影响因子：
3.8
通讯作者：
Uygun BE
中科院分区：
文献类型：
--
作者：
Hafiz EOA;Bulutoglu B;Mansy SS;Chen Y;Abu-Taleb H;Soliman SAM;El-Hindawi AAF;Yarmush ML;Uygun BE
肝组织工程学的目标是创造可移植的肝脏移植物，作为供体肝脏的替代品。构建功能完整的肝组织的一个主要挑战是通过胆小管(BC)与胆管网络的整合来重建工程化肝脏结构中的胆汁引流，从而使胆汁能够从肝细胞清除到宿主十二指肠。在这项研究中，我们展示了通过将大鼠原代肝细胞与胆管细胞和基质细胞共同培养来形成这样的肝脏微组织。我们的结果表明，在球体内，肝细胞维持存活和功能长达7天。存活的肝细胞通过形成BC与紧密连接的存在而极化。在形态上，肝细胞构成球体的核心，而胆管细胞位于外围，形成单层微囊和向外延伸的管状结构。球体随后被成簇培养，以创建类似于肝小叶的更高级别的导管网络。胆管细胞在肝脏球体之间形成功能性胆管通道，能够收集、运输和分泌胆汁。我们的结果构成了通过胆道引流重建肝脏构建块的第一步，以重新填充整个肝支架，用作可移植的肝移植物。
Liver tissue engineering aims to create transplantable liver grafts that can serve as substitutes for donor’s livers. One major challenge in creating a fully functional liver tissue has been to recreate the biliary drainage in an engineered liver construct through integration of bile canaliculi (BC) with the biliary ductular network that would enable the clearance of bile from the hepatocytes to the host duodenum. In this study, we show the formation of such a hepatic microtissue by coculturing rat primary hepatocytes with cholangiocytes and stromal cells. Our results indicate that within the spheroids, hepatocytes maintained viability and function for up to 7 days. Viable hepatocytes became polarized by forming BC with the presence of tight junctions. Morphologically, hepatocytes formed the core of the spheroids, while cholangiocytes resided at the periphery forming a monolayer microcysts and tubular structures extending outward. The spheroids were subsequently cultured in clusters to create a higher order ductular network resembling hepatic lobule. The cholangiocytes formed functional biliary ductular channels in between hepatic spheroids that were able to collect, transport, and secrete bile. Our results constitute the first step to recreate hepatic building blocks with biliary drainage for repopulating the whole liver scaffolds to be used as transplantable liver grafts.
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影响因子：
3.8
作者：
Cho, Chenl H.;Berthiaume, Francois;Tilles, Arno W.;Yarmush, Martin L.
通讯作者：
Yarmush, Martin L.
影响因子：
6.1
作者：
Godoy, Patricio;Hewitt, Nicola J.;Albrecht, Ute;Andersen, Melvin E.;Ansari, Nariman;Bhattacharya, Sudin;Bode, Johannes Georg;Bolleyn, Jennifer;Borner, Christoph;Boettger, Jan;Braeuning, Albert;Budinsky, Robert A.;Burkhardt, Britta;Cameron, Neil R.;Camussi, Giovanni;Cho, Chong-Su;Choi, Yun-Jaie;Rowlands, J. Craig;Dahmen, Uta;Damm, Georg;Dirsch, Olaf;Teresa Donato, Maria;Dong, Jian;Dooley, Steven;Drasdo, Dirk;Eakins, Rowena;Ferreira, Karine Sa;Fonsato, Valentina;Fraczek, Joanna;Gebhardt, Rolf;Gibson, Andrew;Glanemann, Matthias;Goldring, Chris E. P.;Jose Gomez-Lechon, Maria;Groothuis, Geny M. M.;Gustavsson, Lena;Guyot, Christelle;Hallifax, David;Hammad, Seddik;Hayward, Adam;Haeussinger, Dieter;Hellerbrand, Claus;Hewitt, Philip;Hoehme, Stefan;Holzhuetter, Hermann-Georg;Houston, J. Brian;Hrach, Jens;Ito, Kiyomi;Jaeschke, Hartmut;Keitel, Verena;Kelm, Jens M.;Park, B. Kevin;Kordes, Claus;Kullak-Ublick, Gerd A.;LeCluyse, Edward L.;Lu, Peng;Luebke-Wheeler, Jennifer;Lutz, Anna;Maltman, Daniel J.;Matz-Soja, Madlen;McMullen, Patrick;Merfort, Irmgard;Messner, Simon;Meyer, Christoph;Mwinyi, Jessica;Naisbitt, Dean J.;Nussler, Andreas K.;Olinga, Peter;Pampaloni, Francesco;Pi, Jingbo;Pluta, Linda;Przyborski, Stefan A.;Ramachandran, Anup;Rogiers, Vera;Rowe, Cliff;Schelcher, Celine;Schmich, Kathrin;Schwarz, Michael;Singh, Bijay;Stelzer, Ernst H. K.;Stieger, Bruno;Stoeber, Regina;Sugiyama, Yuichi;Tetta, Ciro;Thasler, Wolfgang E.;Vanhaecke, Tamara;Vinken, Mathieu;Weiss, Thomas S.;Widera, Agata;Woods, Courtney G.;Xu, Jinghai James;Yarborough, Kathy M.;Hengstler, Jan G.
通讯作者：
Hengstler, Jan G.
影响因子：
5.6
作者：
Safitri, Astia;Shinohara, Marie;Sakai, Yasuyuki
通讯作者：
Sakai, Yasuyuki
影响因子：
2.7
作者：
Cho CH;Park J;Tilles AW;Berthiaume F;Toner M;Yarmush ML
通讯作者：
Yarmush ML
影响因子：
13.5
作者：
Auth, MKH;Joplin, RE;Strain, AJ
通讯作者：
Strain, AJ