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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/140478
Ver los metadatos del registro completo
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oai:ri.conicet.gov.ar:11336/140478 |
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3498 |
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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 |
_version_ |
1844613265296982016 |
score |
13.070432 |