公开(公告)号：US12129490B2

公开(公告)日：2024-10-29

申请号：US16109202

申请日：2018-08-22

Applicant: UNIVERSITY HEALTH NETWORK ,  THE HOSPITAL FOR SICK CHILDREN

Inventor： Gordon Keller ,  Shinichiro Ogawa ,  Anand Ghanekar ,  Christine Bear ,  Binita M. Kamath ,  Mina Ogawa ,  James Surapisitchat

IPC: C12N5/071 ,  A61K35/407

CPC classification number: C12N5/067 ,  C12N5/0679 ,  A61K35/407 ,  C12N2501/01 ,  C12N2501/115 ,  C12N2501/119 ,  C12N2501/12 ,  C12N2501/155 ,  C12N2501/16 ,  C12N2501/237 ,  C12N2501/415 ,  C12N2501/42 ,  C12N2501/724 ,  C12N2501/727 ,  C12N2501/999 ,  C12N2502/00 ,  C12N2502/14 ,  C12N2503/02 ,  C12N2506/02 ,  C12N2506/45

Abstract: Methods for producing hepatocyte and/or cholangiocyte lineage cells from pluripotent stem cells, the method comprising (a) specifying the extended nodal agonist treated induced endodermal cell population to obtain a cell population comprising hepatocyte and/or cholangiocyte progenitors by contacting the extended nodal agonist treated induced endodermal cell population with specification media comprising a FGF agonist and a BMP4 agonist and/or active conjugates and/or fragments thereof; (b) inducing maturation, and optionally further lineage specification and/or expansion of the hepatocyte and/or cholangiocyte progenitors of the cell population to obtain a population comprising hepatocyte lineage cells such as hepatoblasts, hepatocytes and/or cholangiocytes, the inducing maturation step comprising generating aggregates of the cell population. Optionally, the method also comprises activating the cAMP pathway within the aggregates and forming co-aggregates.