	US 12,441,987 B2
	Multicellular integrated brain tissue in neurological diseases
Li-Huei Tsai, Cambridge, MA (US); Joel Blanchard, Arlington, MA (US); Alice Stanton, Boston, MA (US); Adele Bubnys, Cambridge, MA (US); and Robert S. Langer, Newton, MA (US)
Assigned to Massachusetts Institute of Technology, Cambridge, MA (US)
Filed by Massachusetts Institute of Technology, Cambridge, MA (US)
Filed on Aug. 27, 2021, as Appl. No. 17/458,838.
Claims priority of provisional application 63/106,320, filed on Oct. 27, 2020.
Prior Publication US 2022/0127581 A1, Apr. 28, 2022
Int. Cl. C12N 5/071 (2010.01); A61K 35/30 (2015.01); C12N 5/00 (2006.01); C12N 5/074 (2010.01); C12N 5/079 (2010.01)

CPC C12N 5/0691 (2013.01) [A61K 35/30 (2013.01); C12N 5/0062 (2013.01); C12N 5/0607 (2013.01); C12N 5/0622 (2013.01); C12N 2502/28 (2013.01); C12N 2503/00 (2013.01); C12N 2513/00 (2013.01); C12N 2533/90 (2013.01)]

20 Claims

1. A multi-cellular integrated micro brain (miBRAIN) comprising a 3-dimensional (3D) matrix comprising an interconnected cerebrovascular network comprised of human brain endothelial cell (BEC) vessels positioned in the 3D matrix and comprised of human pluripotent stem cell-derived endothelial cells, human pluripotent stem cell-derived pericytes proximal to the BEC vessel and physically interacting with an apical surface of the BEC vessels, human pluripotent stem cell-derived astrocytes, human myelinated cells, each of which is co-cultured in and dispersed throughout the 3D matrix, and optionally immune cells, wherein the 3D matrix comprises a material selected from the group consisting of an engineered hydrogel, exogenous RGD polymers and dextran.