Innervated organoid compositions and methods of making same
AssigneesThe University of Hong Kong, Children's Hospital Medical Center
InventorsSau-Wai Elly Ngan, James M. Wells
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Abstract
Disclosed are in vitro methods for the differentiation of precursor cells into a neural crest cell (NCC) primed to a neurogenic lineage. The methods may include, for example, the steps of activating a Hedgehog signaling pathway (“HH signaling pathway”) in a precursor cell, wherein the precursor cell may be contacted with a neural crest cell induction medium for differentiation of the precursor cell into a neural crest cell. Compositions for carrying out the disclosed methods are also disclosed.
Claims21
A method of making an innervated colonic organoid model, comprising the step of
- a. activating a Hedgehog signaling pathway (“HH signaling pathway”) in a precursor cell, wherein said precursor cell is contacted with a neural crest cell (“NCC”) induction medium until said precursor cell differentiates into an enteric neural crest cell (ENCC) primed to a neurogenic lineage, and wherein said precursor cell is a pluripotent stem cell;
- b. contacting the ENCC primed to a neurogenic lineage with a hindgut spheroid;
- and
- c. transplanting said hindgut spheroid and said ENCCs primed to a neurogenic lineage into a kidney capsule of an immunodeficient host until an innervated colonic organoid forms;
- wherein said hindgut spheroid is obtained from definitive endoderm.
Dependencies are inferred from the claim text.