Pluripotent stem cell-derived heart organoid
AssigneeBoard of Trustees of Michigan State University
InventorsAitor Aguirre, Yonatan Raz Israeli
Life of this patent
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Abstract
A method for generating a heart organoid is provided. The method includes forming a cellular aggregate of pluripotent stem cells, activating Wnt signaling in the cellular aggregate to cause the cellular aggregate to differentiate into a three-dimensional cardiac mesoderm, and inhibiting the Wnt signaling in the cardiac mesoderm to form the heart organoid. The heart organoid includes myocardial tissue, endocardial tissue defining at least one chamber, and epicardial tissue disposed on at least an outer surface of the myocardial tissue. The heart organoid beats. Heart organoids prepared in accordance with the method are also provided.
Claims18
A method for generating a heart organoid, the method comprising:
- forming a cellular aggregate comprising pluripotent stem cells;
- a first activating step comprising contacting the cellular aggregate with a first Wnt signaling pathway activator to cause the cellular aggregate to differentiate into a three-dimensional cardiac mesoderm, wherein the first Wnt signaling pathway activator is a glycogen synthase kinase 3 (GSK 3) inhibitor;
- and
- contacting the three-dimensional cardiac mesoderm with a Wnt signaling pathway inhibitor to form the heart organoid, wherein the Wnt signaling pathway inhibitor is a Porcupine (PORCN) inhibitor;
- wherein the heart organoid comprises myocardial tissue, endocardial tissue defining at least one cardiac chamber, and epicardial tissue disposed on at least an outer surface of the myocardial tissue;
- and
- wherein the heart organoid beats;
- and
- wherein the heart organoid is generated without embedding cells in a hydrogel matrix.
An in vitro generated heart organoid comprising:
- a three-dimensional body having an interior portion and an outer surface, the interior portion comprising myocardial tissue;
- endocardial cells defining at least one cardiac chamber within the myocardial tissue, wherein the at least one cardiac chamber is not in fluid communication with veins or arteries that correspond to those of a naturally occurring heart;
- and
- epicardial tissue disposed on at least a portion of the outer surface;
- wherein the heart organoid beats;
- and
- wherein the heart organoid is derived from cultured pluripotent stem cells.
Dependencies are inferred from the claim text.