Complex bile duct network formation within liver decellularized extracellular matrix hydrogels

Abstract The biliary tree is an essential component of transplantable human liver tissue. Despite recent advances in liver tissue engineering, attempts at re-creating the intrahepatic biliary tree have not progressed significantly. The finer branches of the biliary tree are structurally and function...

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Autores principales:	Phillip L. Lewis, Jimmy Su, Ming Yan, Fanyin Meng, Shannon S. Glaser, Gianfranco D. Alpini, Richard M. Green, Beatriz Sosa-Pineda, Ramille N. Shah
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/456249077e1a4cbbbbc9bd397904fcf4
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spelling	oai:doaj.org-article:456249077e1a4cbbbbc9bd397904fcf42021-12-02T15:09:08ZComplex bile duct network formation within liver decellularized extracellular matrix hydrogels10.1038/s41598-018-30433-62045-2322https://doaj.org/article/456249077e1a4cbbbbc9bd397904fcf42018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-30433-6https://doaj.org/toc/2045-2322Abstract The biliary tree is an essential component of transplantable human liver tissue. Despite recent advances in liver tissue engineering, attempts at re-creating the intrahepatic biliary tree have not progressed significantly. The finer branches of the biliary tree are structurally and functionally complex and heterogeneous and require harnessing innate developmental processes for their regrowth. Here we demonstrate the ability of decellularized liver extracellular matrix (dECM) hydrogels to induce the in vitro formation of complex biliary networks using encapsulated immortalized mouse small biliary epithelial cells (cholangiocytes). This phenomenon is not observed using immortalized mouse large cholangiocytes, or with purified collagen 1 gels or Matrigel. We also show phenotypic stability via immunostaining for specific cholangiocyte markers. Moreover, tight junction formation and maturation was observed to occur between cholangiocytes, exhibiting polarization and transporter activity. To better define the mechanism of duct formation, we utilized three fluorescently labeled, but otherwise identical populations of cholangiocytes. The cells, in a proximity dependent manner, either branch out clonally, radiating from a single nucleation point, or assemble into multi-colored structures arising from separate populations. These findings present liver dECM as a promising biomaterial for intrahepatic bile duct tissue engineering and as a tool to study duct remodeling in vitro.Phillip L. LewisJimmy SuMing YanFanyin MengShannon S. GlaserGianfranco D. AlpiniRichard M. GreenBeatriz Sosa-PinedaRamille N. ShahNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Phillip L. Lewis Jimmy Su Ming Yan Fanyin Meng Shannon S. Glaser Gianfranco D. Alpini Richard M. Green Beatriz Sosa-Pineda Ramille N. Shah Complex bile duct network formation within liver decellularized extracellular matrix hydrogels
description	Abstract The biliary tree is an essential component of transplantable human liver tissue. Despite recent advances in liver tissue engineering, attempts at re-creating the intrahepatic biliary tree have not progressed significantly. The finer branches of the biliary tree are structurally and functionally complex and heterogeneous and require harnessing innate developmental processes for their regrowth. Here we demonstrate the ability of decellularized liver extracellular matrix (dECM) hydrogels to induce the in vitro formation of complex biliary networks using encapsulated immortalized mouse small biliary epithelial cells (cholangiocytes). This phenomenon is not observed using immortalized mouse large cholangiocytes, or with purified collagen 1 gels or Matrigel. We also show phenotypic stability via immunostaining for specific cholangiocyte markers. Moreover, tight junction formation and maturation was observed to occur between cholangiocytes, exhibiting polarization and transporter activity. To better define the mechanism of duct formation, we utilized three fluorescently labeled, but otherwise identical populations of cholangiocytes. The cells, in a proximity dependent manner, either branch out clonally, radiating from a single nucleation point, or assemble into multi-colored structures arising from separate populations. These findings present liver dECM as a promising biomaterial for intrahepatic bile duct tissue engineering and as a tool to study duct remodeling in vitro.
format	article
author	Phillip L. Lewis Jimmy Su Ming Yan Fanyin Meng Shannon S. Glaser Gianfranco D. Alpini Richard M. Green Beatriz Sosa-Pineda Ramille N. Shah
author_facet	Phillip L. Lewis Jimmy Su Ming Yan Fanyin Meng Shannon S. Glaser Gianfranco D. Alpini Richard M. Green Beatriz Sosa-Pineda Ramille N. Shah
author_sort	Phillip L. Lewis
title	Complex bile duct network formation within liver decellularized extracellular matrix hydrogels
title_short	Complex bile duct network formation within liver decellularized extracellular matrix hydrogels
title_full	Complex bile duct network formation within liver decellularized extracellular matrix hydrogels
title_fullStr	Complex bile duct network formation within liver decellularized extracellular matrix hydrogels
title_full_unstemmed	Complex bile duct network formation within liver decellularized extracellular matrix hydrogels
title_sort	complex bile duct network formation within liver decellularized extracellular matrix hydrogels
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/456249077e1a4cbbbbc9bd397904fcf4
work_keys_str_mv	AT phillipllewis complexbileductnetworkformationwithinliverdecellularizedextracellularmatrixhydrogels AT jimmysu complexbileductnetworkformationwithinliverdecellularizedextracellularmatrixhydrogels AT mingyan complexbileductnetworkformationwithinliverdecellularizedextracellularmatrixhydrogels AT fanyinmeng complexbileductnetworkformationwithinliverdecellularizedextracellularmatrixhydrogels AT shannonsglaser complexbileductnetworkformationwithinliverdecellularizedextracellularmatrixhydrogels AT gianfrancodalpini complexbileductnetworkformationwithinliverdecellularizedextracellularmatrixhydrogels AT richardmgreen complexbileductnetworkformationwithinliverdecellularizedextracellularmatrixhydrogels AT beatrizsosapineda complexbileductnetworkformationwithinliverdecellularizedextracellularmatrixhydrogels AT ramillenshah complexbileductnetworkformationwithinliverdecellularizedextracellularmatrixhydrogels
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Complex bile duct network formation within liver decellularized extracellular matrix hydrogels

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