TY - JOUR
T1 - Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells
AU - Takeishi, Kazuki
AU - Collin de l'Hortet, Alexandra
AU - Wang, Yang
AU - Handa, Kan
AU - Guzman-Lepe, Jorge
AU - Matsubara, Kentaro
AU - Morita, Kazutoyo
AU - Jang, Sae
AU - Haep, Nils
AU - Florentino, Rodrigo M.
AU - Yuan, Fangchao
AU - Fukumitsu, Ken
AU - Tobita, Kimimasa
AU - Sun, Wendell
AU - Franks, Jonathan
AU - Delgado, Evan R.
AU - Shapiro, Erik M.
AU - Fraunhoffer, Nicolas A.
AU - Duncan, Andrew W.
AU - Yagi, Hiroshi
AU - Mashimo, Tomoji
AU - Fox, Ira J.
AU - Soto-Gutierrez, Alejandro
PY - 2020/6/2
Y1 - 2020/6/2
N2 - 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.
AB - 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.
KW - bioengineered human liver
KW - human iPS cells
KW - human iPS-biliary cells
KW - human iPS-endothelial cells
KW - human iPS-hepatocytes
KW - liver maturation
KW - mini human liver
KW - organ-microenvironment
KW - transplantation
UR - http://www.scopus.com/inward/record.url?scp=85085547431&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85085547431&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2020.107711
DO - 10.1016/j.celrep.2020.107711
M3 - Article
C2 - 32492423
AN - SCOPUS:85085547431
VL - 31
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 9
M1 - 107711
ER -