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Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells.
Takeishi, Kazuki; Collin de l'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, Nicolas A; Duncan, Andrew W; Yagi, Hiroshi; Mashimo, Tomoji; Fox, Ira J; Soto-Gutierrez, Alejandro.
Afiliação
  • Takeishi K; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
  • Collin de l'Hortet A; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  • Wang Y; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China.
  • Handa K; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  • Guzman-Lepe J; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  • Matsubara K; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  • Morita K; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  • Jang S; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  • Haep N; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  • Florentino RM; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Physiology and Biophysics, Universidade Federal de Minas Gerais, Belo Horizonte 31270-010, Brazil.
  • Yuan F; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
  • Fukumitsu K; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  • Tobita K; Department of Bioengineering and Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA 15201, USA.
  • Sun W; LifeCell Corporation, Branchburg, NJ 08876, USA.
  • Franks J; Center for Biologic Imaging, University of Pittsburgh Medical School, Pittsburgh, PA 15261, USA.
  • Delgado ER; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219-3110, USA; Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  • Shapiro EM; Department of Radiology, Michigan State University, East Lansing, MI 48824, USA.
  • Fraunhoffer NA; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Facultad de Ciencias de la Salud, Carrera de Medicina, Universidad Maimónides, Ciudad Autónoma de Buenos Aires and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Buen
  • Duncan AW; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219-3110, USA; Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  • Yagi H; Department of Surgery, School of Medicine, Keio University, Tokyo 160-8582, Japan.
  • Mashimo T; Division of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo 158-8557, Japan.
  • Fox IJ; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219-3110, USA; Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Surgery, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA 152
  • Soto-Gutierrez A; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219-3110, USA; Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA 15213, USA. Electronic address: als208@pitt.
Cell Rep ; 31(9): 107711, 2020 06 02.
Article em En | MEDLINE | ID: mdl-32492423
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hepatócitos / Engenharia Tecidual Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hepatócitos / Engenharia Tecidual Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2020 Tipo de documento: Article