US 12,123,026 B2
Human pluripotent stem cell-derived brain organoids for cancer modeling and drug screening
Elizabeth Anne Aisenbrey, Madison, WI (US); William Leo Murphy, Waunakee, WI (US); Elizabeth Emma Torr, Madison, WI (US); Victoria Harms, Madison, WI (US); and Gaurav Kaushik, Madison, WI (US)
Assigned to WISCONSIN ALUMNI RESEARCH FOUNDATION, Madison, WI (US)
Filed by Wisconsin Alumni Research Foundation, Madison, WI (US)
Filed on Mar. 26, 2020, as Appl. No. 16/831,017.
Claims priority of provisional application 62/828,161, filed on Apr. 2, 2019.
Prior Publication US 2020/0318075 A1, Oct. 8, 2020
Int. Cl. C12N 5/09 (2010.01)
CPC C12N 5/0693 (2013.01) [C12N 2500/50 (2013.01); C12N 2501/734 (2013.01); C12N 2501/998 (2013.01); C12N 2502/086 (2013.01); C12N 2502/088 (2013.01); C12N 2502/28 (2013.01); C12N 2502/30 (2013.01)] 16 Claims
 
1. A method of producing a substantially planar vascularized brain cancer organoid, comprising
(a) contacting a plurality of human cells to a substantially planar hydrogel, wherein the hydrogel comprises an RGD-containing peptide and a matrix metalloproteinase (MMP)-sensitive peptide, the plurality of human cells comprising neural progenitor cells, endothelial cells, pericytes, and microglia, wherein neural progenitor cells comprise approximately half of the plurality of cells, endothelial cells comprise approximately 40% of the plurality of cells, pericytes comprise approximately 8% of the plurality of cells and microglia comprise approximately 1% of the plurality of cells;
(b) culturing the contacted hydrogel for at least 7 days until a hydrogel comprising neurons, glia, and vasculature is obtained;
(c) contacting cancer cells to the cultured hydrogel of (b); and
(d) culturing the cancer cell-contacted hydrogel under culture conditions that promote cancer cell proliferation, whereby a vascularized brain cancer organoid comprising a plurality of cancer cells is obtained.