Specification of functional cranial placode derivatives from human pluripotent stem cells

US10273452B2 · kind B2 · utility

Assignee

• Memorial Sloan Kettering Cancer Center · US

Inventors

• Stuart Chambers · San Francisco, US
• Lorenz Studer · New York, US
• Zehra Dincer · New York, US
• Bastian Zimmer · Lindenberg im Allgäu, DE

Key dates

• Filing date: May 19, 2016
• Grant date: Apr 30, 2019
• Expiry date: May 19, 2036

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2506/45
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Cranial placodes are embryonic structures essential for sensory and endocrine organ development. The efficient derivation of cranial placodes from human pluripotent stem cells is disclosed where the timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Further fate specification at the pre-placode stage enables the selective generation of placode-derived trigeminal ganglia capable of in vivo engraftment, mature lens fibers and anterior pituitary hormone-producing cells that upon transplantation produce hormones including, but not limited to, human growth hormone and adrenocortiocotropic hormone in vivo. Alternatively, anterior pituitary hormone-producing cells are generated in cell culture systems in vitro.