US 12,134,785 B2
Differentiation of pluripotent stem cells to form renal organoids
Minoru Takasato, Moonee Ponds (AU); and Melissa Little, Coburg (AU)
Assigned to The University of Queensland, St. Lucia (AU)
Filed by The University of Queensland, St. Lucia (AU)
Filed on Nov. 13, 2019, as Appl. No. 16/682,541.
Application 16/682,541 is a continuation of application No. 15/536,018, abandoned, previously published as PCT/AU2015/050798, filed on Dec. 15, 2015.
Claims priority of application No. 2014277667 (AU), filed on Dec. 15, 2014.
Prior Publication US 2020/0339957 A1, Oct. 29, 2020
Int. Cl. C12N 5/071 (2010.01); C12N 5/074 (2010.01)
CPC C12N 5/0687 (2013.01) [C12N 5/0686 (2013.01); C12N 5/0696 (2013.01); C12N 2501/119 (2013.01); C12N 2501/155 (2013.01); C12N 2501/16 (2013.01); C12N 2501/385 (2013.01); C12N 2501/415 (2013.01); C12N 2506/02 (2013.01); C12N 2506/45 (2013.01)] 24 Claims
 
1. A method of producing one or more renal organoids comprising:
(a) differentiating intermediate mesoderm (IM) cells into nephron progenitor cells and ureteric epithelial progenitor cells by contacting the IM cells with a Wnt agonist, fibroblast growth factor 9 (FGF9), and one or more compounds selected from the group consisting of bone morphogenic protein 7 (BMP7), heparin, retinoic acid (RA), an RA analog, an RA agonist, and an RA antagonist, wherein the RA antagonist increases the relative production of nephron progenitor cells from the IM cells; and
(b) culturing the nephron progenitor cells and ureteric epithelial progenitor cells under conditions that induce aggregation of the nephron progenitor cells and ureteric epithelial progenitor cells into one or more renal organoids that are at least partly vascularized and/or comprise vascular progenitors, wherein the vascularization is facilitated by conditions that promote or direct development of vascular endothelium or vascular progenitors from mesenchymal cells or tissues.