Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells

Autores
Takeishi, Kazuki; Collin de I'Hortet, Alexandra; Wang, Yang; Handa, Kan; Guzman Lepe, Jorge; Matsubara, Kentaro; Morita, Kazutoyo; Jang, Sae; Haep, Nils; Florentino, Rodrigo M.; Yuan, Fangchao; Fukumitsu, Ken; Tobita, Kimimasa; Sun, Wendell; Franks, Jonathan; Delgado, Evan R.; Shapiro, Erik M.; Fraunhoffer Navarro, Nicolas Alejandro; Duncan, Andrew W.; Yagi, Hiroshi; Mashimo, Tomoji; Fox, Ira J.; Soto Gutierrez, Alejandro
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The availability of an autologous transplantable auxiliary liver would dramatically affect the treatment of liver disease. Assembly and function in vivo of a bioengineered human liver derived from induced pluripotent stem cells (iPSCs) has not been previously described. By improving methods for liver decellularization, recellularization, and differentiation of different liver cellular lineages of human iPSCs in an organ-like environment, we generated functional engineered human mini livers and performed transplantation in a rat model. Whereas previous studies recellularized liver scaffolds largely with rodent hepatocytes, we repopulated not only the parenchyma with human iPSC-hepatocytes but also the vascular system with human iPS-endothelial cells, and the bile duct network with human iPSC-biliary epithelial cells. The regenerated human iPSC-derived mini liver containing multiple cell types was tested in vivo and remained functional for 4 days after auxiliary liver transplantation in immunocompromised, engineered (IL2rg−/−) rats.
Fil: Takeishi, Kazuki. University of Pittsburgh; Estados Unidos
Fil: Collin de I'Hortet, Alexandra. University of Pittsburgh; Estados Unidos
Fil: Wang, Yang. University of Pittsburgh; Estados Unidos
Fil: Handa, Kan. University of Pittsburgh; Estados Unidos
Fil: Guzman Lepe, Jorge. University of Pittsburgh; Estados Unidos
Fil: Matsubara, Kentaro. University of Pittsburgh; Estados Unidos
Fil: Morita, Kazutoyo. University of Pittsburgh; Estados Unidos
Fil: Jang, Sae. University of Pittsburgh; Estados Unidos
Fil: Haep, Nils. University of Pittsburgh; Estados Unidos
Fil: Florentino, Rodrigo M.. University of Pittsburgh; Estados Unidos
Fil: Yuan, Fangchao. University of Pittsburgh; Estados Unidos
Fil: Fukumitsu, Ken. University of Pittsburgh; Estados Unidos
Fil: Tobita, Kimimasa. University of Pittsburgh; Estados Unidos
Fil: Sun, Wendell. University of Pittsburgh; Estados Unidos
Fil: Franks, Jonathan. University of Pittsburgh; Estados Unidos
Fil: Delgado, Evan R.. University of Pittsburgh; Estados Unidos
Fil: Shapiro, Erik M.. University of Pittsburgh; Estados Unidos
Fil: Fraunhoffer Navarro, Nicolas Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Duncan, Andrew W.. University of Pittsburgh; Estados Unidos
Fil: Yagi, Hiroshi. University of Pittsburgh; Estados Unidos
Fil: Mashimo, Tomoji. University of Pittsburgh; Estados Unidos
Fil: Fox, Ira J.. University of Pittsburgh; Estados Unidos
Fil: Soto Gutierrez, Alejandro. University of Pittsburgh; Estados Unidos
Materia
BIOENGINEERED HUMAN LIVER
HUMAN IPS CELLS
HUMAN IPS-BILIARY CELLS
HUMAN IPS-ENDOTHELIAL CELLS
HUMAN IPS-HEPATOCYTES
LIVER MATURATION
MINI HUMAN LIVER
ORGAN-MICROENVIRONMENT
TRANSPLANTATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/140478

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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem CellsTakeishi, KazukiCollin de I'Hortet, AlexandraWang, YangHanda, KanGuzman Lepe, JorgeMatsubara, KentaroMorita, KazutoyoJang, SaeHaep, NilsFlorentino, Rodrigo M.Yuan, FangchaoFukumitsu, KenTobita, KimimasaSun, WendellFranks, JonathanDelgado, Evan R.Shapiro, Erik M.Fraunhoffer Navarro, Nicolas AlejandroDuncan, Andrew W.Yagi, HiroshiMashimo, TomojiFox, Ira J.Soto Gutierrez, AlejandroBIOENGINEERED HUMAN LIVERHUMAN IPS CELLSHUMAN IPS-BILIARY CELLSHUMAN IPS-ENDOTHELIAL CELLSHUMAN IPS-HEPATOCYTESLIVER MATURATIONMINI HUMAN LIVERORGAN-MICROENVIRONMENTTRANSPLANTATIONhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The availability of an autologous transplantable auxiliary liver would dramatically affect the treatment of liver disease. Assembly and function in vivo of a bioengineered human liver derived from induced pluripotent stem cells (iPSCs) has not been previously described. By improving methods for liver decellularization, recellularization, and differentiation of different liver cellular lineages of human iPSCs in an organ-like environment, we generated functional engineered human mini livers and performed transplantation in a rat model. Whereas previous studies recellularized liver scaffolds largely with rodent hepatocytes, we repopulated not only the parenchyma with human iPSC-hepatocytes but also the vascular system with human iPS-endothelial cells, and the bile duct network with human iPSC-biliary epithelial cells. The regenerated human iPSC-derived mini liver containing multiple cell types was tested in vivo and remained functional for 4 days after auxiliary liver transplantation in immunocompromised, engineered (IL2rg−/−) rats.Fil: Takeishi, Kazuki. University of Pittsburgh; Estados UnidosFil: Collin de I'Hortet, Alexandra. University of Pittsburgh; Estados UnidosFil: Wang, Yang. University of Pittsburgh; Estados UnidosFil: Handa, Kan. University of Pittsburgh; Estados UnidosFil: Guzman Lepe, Jorge. University of Pittsburgh; Estados UnidosFil: Matsubara, Kentaro. University of Pittsburgh; Estados UnidosFil: Morita, Kazutoyo. University of Pittsburgh; Estados UnidosFil: Jang, Sae. University of Pittsburgh; Estados UnidosFil: Haep, Nils. University of Pittsburgh; Estados UnidosFil: Florentino, Rodrigo M.. University of Pittsburgh; Estados UnidosFil: Yuan, Fangchao. University of Pittsburgh; Estados UnidosFil: Fukumitsu, Ken. University of Pittsburgh; Estados UnidosFil: Tobita, Kimimasa. University of Pittsburgh; Estados UnidosFil: Sun, Wendell. University of Pittsburgh; Estados UnidosFil: Franks, Jonathan. University of Pittsburgh; Estados UnidosFil: Delgado, Evan R.. University of Pittsburgh; Estados UnidosFil: Shapiro, Erik M.. University of Pittsburgh; Estados UnidosFil: Fraunhoffer Navarro, Nicolas Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Duncan, Andrew W.. University of Pittsburgh; Estados UnidosFil: Yagi, Hiroshi. University of Pittsburgh; Estados UnidosFil: Mashimo, Tomoji. University of Pittsburgh; Estados UnidosFil: Fox, Ira J.. University of Pittsburgh; Estados UnidosFil: Soto Gutierrez, Alejandro. University of Pittsburgh; Estados UnidosCell Press2020-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/140478Takeishi, Kazuki; Collin de I'Hortet, Alexandra; Wang, Yang; Handa, Kan; Guzman Lepe, Jorge; et al.; Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells; Cell Press; Cell Reports; 31; 9; 6-2020; 1-302211-1247CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S2211124720306884info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2020.107711info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:40:00Zoai:ri.conicet.gov.ar:11336/140478instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:40:00.563CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells
title Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells
spellingShingle Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells
Takeishi, Kazuki
BIOENGINEERED HUMAN LIVER
HUMAN IPS CELLS
HUMAN IPS-BILIARY CELLS
HUMAN IPS-ENDOTHELIAL CELLS
HUMAN IPS-HEPATOCYTES
LIVER MATURATION
MINI HUMAN LIVER
ORGAN-MICROENVIRONMENT
TRANSPLANTATION
title_short Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells
title_full Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells
title_fullStr Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells
title_full_unstemmed Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells
title_sort Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells
dc.creator.none.fl_str_mv Takeishi, Kazuki
Collin de I'Hortet, Alexandra
Wang, Yang
Handa, Kan
Guzman Lepe, Jorge
Matsubara, Kentaro
Morita, Kazutoyo
Jang, Sae
Haep, Nils
Florentino, Rodrigo M.
Yuan, Fangchao
Fukumitsu, Ken
Tobita, Kimimasa
Sun, Wendell
Franks, Jonathan
Delgado, Evan R.
Shapiro, Erik M.
Fraunhoffer Navarro, Nicolas Alejandro
Duncan, Andrew W.
Yagi, Hiroshi
Mashimo, Tomoji
Fox, Ira J.
Soto Gutierrez, Alejandro
author Takeishi, Kazuki
author_facet Takeishi, Kazuki
Collin de I'Hortet, Alexandra
Wang, Yang
Handa, Kan
Guzman Lepe, Jorge
Matsubara, Kentaro
Morita, Kazutoyo
Jang, Sae
Haep, Nils
Florentino, Rodrigo M.
Yuan, Fangchao
Fukumitsu, Ken
Tobita, Kimimasa
Sun, Wendell
Franks, Jonathan
Delgado, Evan R.
Shapiro, Erik M.
Fraunhoffer Navarro, Nicolas Alejandro
Duncan, Andrew W.
Yagi, Hiroshi
Mashimo, Tomoji
Fox, Ira J.
Soto Gutierrez, Alejandro
author_role author
author2 Collin de I'Hortet, Alexandra
Wang, Yang
Handa, Kan
Guzman Lepe, Jorge
Matsubara, Kentaro
Morita, Kazutoyo
Jang, Sae
Haep, Nils
Florentino, Rodrigo M.
Yuan, Fangchao
Fukumitsu, Ken
Tobita, Kimimasa
Sun, Wendell
Franks, Jonathan
Delgado, Evan R.
Shapiro, Erik M.
Fraunhoffer Navarro, Nicolas Alejandro
Duncan, Andrew W.
Yagi, Hiroshi
Mashimo, Tomoji
Fox, Ira J.
Soto Gutierrez, Alejandro
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BIOENGINEERED HUMAN LIVER
HUMAN IPS CELLS
HUMAN IPS-BILIARY CELLS
HUMAN IPS-ENDOTHELIAL CELLS
HUMAN IPS-HEPATOCYTES
LIVER MATURATION
MINI HUMAN LIVER
ORGAN-MICROENVIRONMENT
TRANSPLANTATION
topic BIOENGINEERED HUMAN LIVER
HUMAN IPS CELLS
HUMAN IPS-BILIARY CELLS
HUMAN IPS-ENDOTHELIAL CELLS
HUMAN IPS-HEPATOCYTES
LIVER MATURATION
MINI HUMAN LIVER
ORGAN-MICROENVIRONMENT
TRANSPLANTATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The availability of an autologous transplantable auxiliary liver would dramatically affect the treatment of liver disease. Assembly and function in vivo of a bioengineered human liver derived from induced pluripotent stem cells (iPSCs) has not been previously described. By improving methods for liver decellularization, recellularization, and differentiation of different liver cellular lineages of human iPSCs in an organ-like environment, we generated functional engineered human mini livers and performed transplantation in a rat model. Whereas previous studies recellularized liver scaffolds largely with rodent hepatocytes, we repopulated not only the parenchyma with human iPSC-hepatocytes but also the vascular system with human iPS-endothelial cells, and the bile duct network with human iPSC-biliary epithelial cells. The regenerated human iPSC-derived mini liver containing multiple cell types was tested in vivo and remained functional for 4 days after auxiliary liver transplantation in immunocompromised, engineered (IL2rg−/−) rats.
Fil: Takeishi, Kazuki. University of Pittsburgh; Estados Unidos
Fil: Collin de I'Hortet, Alexandra. University of Pittsburgh; Estados Unidos
Fil: Wang, Yang. University of Pittsburgh; Estados Unidos
Fil: Handa, Kan. University of Pittsburgh; Estados Unidos
Fil: Guzman Lepe, Jorge. University of Pittsburgh; Estados Unidos
Fil: Matsubara, Kentaro. University of Pittsburgh; Estados Unidos
Fil: Morita, Kazutoyo. University of Pittsburgh; Estados Unidos
Fil: Jang, Sae. University of Pittsburgh; Estados Unidos
Fil: Haep, Nils. University of Pittsburgh; Estados Unidos
Fil: Florentino, Rodrigo M.. University of Pittsburgh; Estados Unidos
Fil: Yuan, Fangchao. University of Pittsburgh; Estados Unidos
Fil: Fukumitsu, Ken. University of Pittsburgh; Estados Unidos
Fil: Tobita, Kimimasa. University of Pittsburgh; Estados Unidos
Fil: Sun, Wendell. University of Pittsburgh; Estados Unidos
Fil: Franks, Jonathan. University of Pittsburgh; Estados Unidos
Fil: Delgado, Evan R.. University of Pittsburgh; Estados Unidos
Fil: Shapiro, Erik M.. University of Pittsburgh; Estados Unidos
Fil: Fraunhoffer Navarro, Nicolas Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Duncan, Andrew W.. University of Pittsburgh; Estados Unidos
Fil: Yagi, Hiroshi. University of Pittsburgh; Estados Unidos
Fil: Mashimo, Tomoji. University of Pittsburgh; Estados Unidos
Fil: Fox, Ira J.. University of Pittsburgh; Estados Unidos
Fil: Soto Gutierrez, Alejandro. University of Pittsburgh; Estados Unidos
description The availability of an autologous transplantable auxiliary liver would dramatically affect the treatment of liver disease. Assembly and function in vivo of a bioengineered human liver derived from induced pluripotent stem cells (iPSCs) has not been previously described. By improving methods for liver decellularization, recellularization, and differentiation of different liver cellular lineages of human iPSCs in an organ-like environment, we generated functional engineered human mini livers and performed transplantation in a rat model. Whereas previous studies recellularized liver scaffolds largely with rodent hepatocytes, we repopulated not only the parenchyma with human iPSC-hepatocytes but also the vascular system with human iPS-endothelial cells, and the bile duct network with human iPSC-biliary epithelial cells. The regenerated human iPSC-derived mini liver containing multiple cell types was tested in vivo and remained functional for 4 days after auxiliary liver transplantation in immunocompromised, engineered (IL2rg−/−) rats.
publishDate 2020
dc.date.none.fl_str_mv 2020-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/140478
Takeishi, Kazuki; Collin de I'Hortet, Alexandra; Wang, Yang; Handa, Kan; Guzman Lepe, Jorge; et al.; Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells; Cell Press; Cell Reports; 31; 9; 6-2020; 1-30
2211-1247
CONICET Digital
CONICET
url http://hdl.handle.net/11336/140478
identifier_str_mv Takeishi, Kazuki; Collin de I'Hortet, Alexandra; Wang, Yang; Handa, Kan; Guzman Lepe, Jorge; et al.; Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells; Cell Press; Cell Reports; 31; 9; 6-2020; 1-30
2211-1247
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S2211124720306884
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2020.107711
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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