Compositions and methods for obtaining 3-dimensional lung-like epithelium and related uses thereof
AssigneeThe Regents of the University of Michigan
InventorsJason Spence, Alyssa Miller
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Abstract
The invention disclosed herein generally relates to methods and systems for growing, expanding and/or obtaining 3-dimensional lung-like epithelium comprising cells having SOX9 protein activity and SOX2+ protein activity. In particular, the invention disclosed herein relates to methods and systems for growing human cells having SOX9 protein activity and SOX2+ protein activity in vitro, and for promoting pluripotent stem cell derived ventral-anterior foregut spheroid tissue into 3-dimensional lung-like epithelium comprising cells having SOX9 protein activity and SOX2+ protein activity.
Claims11
A method, comprising:
- culturing in vitro for approximately forty days cells from NKX2.1+ ventral-anterior foregut spheroid tissue derived from pluripotent stem cells, wherein the culturing results in differentiation of the cells from the NKX2.1+ ventral-anterior foregut spheroid tissue derived from pluripotent stem cells into tissue comprising 3-dimensional lung-like epithelium, wherein the culturing comprises activating the FGF signaling pathway, the retinoic acid signaling pathway, and the Wnt signaling pathway;
- and
- obtaining 3-dimensional lung tissue from the cultured tissue comprising 3-dimensional lung-like epithelium, wherein the obtained 3-dimensional lung tissue comprises a 3-dimensional lung tissue peripheral region and a 3-dimenstional lung tissue internal region,
- wherein the 3-dimensional lung tissue peripheral region comprises cells expressing SOX9 protein and SOX2 protein,
- wherein the 3-dimensional lung tissue internal region comprises cells expressing SOX2 protein, SCGB1A1 protein, and MUC5AC, wherein the 3-dimensional lung tissue internal region does not comprise cells expressing SOX9 protein.
A method of treating a mammalian subject having a damaged lung tissue with reduced function, comprising:
- a) culturing in vitro for approximately forty days cells from NKX2.1+ ventral-anterior foregut spheroid tissue derived from pluripotent stem cells, wherein the culturing results in differentiation of the obtained NKX2.1+ ventral-anterior foregut spheroid tissue into tissue comprising 3-dimensional lung-like epithelium, wherein the culturing comprises activating the FGF signaling pathway, the retinoic acid signaling pathway, and the Wnt signaling pathway;
- b) obtaining 3-dimensional lung tissue from the cultured tissue comprising 3-dimensional lung-like epithelium, wherein the obtained 3-dimensional lung tissue comprises a 3-dimensional lung tissue peripheral region and a 3-dimensional lung tissue internal region,
- wherein the 3-dimensional lung tissue peripheral region comprises cells expressing SOX9 protein and SOX2 protein,
- wherein the 3-dimensional lung tissue internal region comprises cells expressing SOX2 protein, SCGB1A1 protein, and MUC5AC, wherein the 3-dimensional lung tissue internal region does not have cells expressing SOX9 protein;
- c) engrafting the obtained 3-dimensional lung tissue at the site of injury, wherein engrafted 3-dimensional lung tissue engraft at the site of injury and repopulate at least a portion of the site with the engrafted cells, wherein the repopulated cells supplement the function, thereby treating the subject.
Dependencies are inferred from the claim text.