US 12,281,332 B2
Methods of enhancing development of renal organoids and methods of using the same
Kimberly A. Homan, Somerville, MA (US); Navin R. Gupta, Brighton, MA (US); Katharina T. Kroll, Boston, MA (US); David B. Kolesky, Cambridge, MA (US); Mark Skylar-Scott, Brookline, MA (US); Michael T. Valerius, Belmont, MA (US); Joseph Bonventre, Wayland, MA (US); Ryuji Morizane, Brookline, MA (US); and Jennifer Lewis, Cambridge, MA (US)
Assigned to PRESIDENT AND FELLOWS OF HARVARD COLLEGE, Cambridge, MA (US); and THE BRIGHAM AND WOMEN'S HOSPITAL, INC., Boston, MA (US)
Appl. No. 16/620,225
Filed by President and Fellows of Harvard College, Cambridge, MA (US); and The Brigham And Women's Hospital, Inc., Boston, MA (US)
PCT Filed Jun. 8, 2018, PCT No. PCT/US2018/036677
§ 371(c)(1), (2) Date Dec. 6, 2019,
PCT Pub. No. WO2018/227101, PCT Pub. Date Dec. 13, 2018.
Claims priority of provisional application 62/517,536, filed on Jun. 9, 2017.
Prior Publication US 2020/0248147 A1, Aug. 6, 2020
Int. Cl. C12N 5/071 (2010.01); A61K 35/22 (2015.01); G01N 33/50 (2006.01)
CPC C12N 5/0686 (2013.01) [A61K 35/22 (2013.01); G01N 33/5082 (2013.01); C12N 2500/00 (2013.01); C12N 2501/119 (2013.01); C12N 2503/04 (2013.01); C12N 2506/02 (2013.01); C12N 2506/45 (2013.01); C12N 2513/00 (2013.01); C12N 2521/00 (2013.01); C12N 2533/52 (2013.01); C12N 2533/54 (2013.01); C12N 2533/56 (2013.01); C12N 2533/90 (2013.01); G01N 2500/10 (2013.01)] 15 Claims
 
1. A method of generating a vascularized renal tissue construct or renal organoid, comprising:
providing a developing renal tissue construct or renal organoid; and
exposing at least a portion of at least the outer surface of the developing renal tissue construct or renal organoid to fluid perfusion to impart fluidic shear stress (FSS) to induce vascularization and glomerular and tubular maturation in the developing renal tissue construct or renal organoid,
wherein the FSS is pulsed to mimic blood pressure changes during regular heart beats or wherein the FSS is intermittent;
thereby producing the vascularized renal tissue construct or renal organoid.