Differentiation of human ips cells to human alveolar type ii via definitive endoderm

Abstract

The present invention relates to compositions and methods for generating populations of tissue precursor cells from pluripotent cells, and preferably induction of stem cells into definitive endoderm to generate anterior foregut endoderm from pluripotent cells. The anterior foregut endoderm cells can then be differentiated into an alveolar epithelial type II cell.

1 - 11 . (canceled) 
     
     
         12 . A population of lung cells produced by a method of differentiating a stem cell into a lung cell, the method comprising: a) inducing a stem cell into a definitive endoderm cell; b) inducing the definitive endoderm cell into an anterior foregut endoderm cell; c) inducing the anterior foregut endoderm cell into a lung cell, thereby differentiating a stem cell into a lung cell. 
     
     
         13 . The population lung cells of  claim 12 , wherein the population is at least 95% of cells exhibiting an alveolar type II phenotype. 
     
     
         14 . The population of lung cells of  claim 13 , wherein the alveolar type II phenotype is expression of an alveolar type II cell marker selected from the group consisting of SPC, Mucin-1, SPB, CD54, and any combination thereof. 
     
     
         15 . The population of lung cells of  claim 12 , wherein the population comprises genetically modified cells. 
     
     
         16 . The population of lung cells of  claim 12 , wherein the cells are genetically modified to express a therapeutic gene. 
     
     
         17 . The population of lungs cells of  claim 12 , wherein the cells resemble freshly isolated human primary alveolar type II cells. 
     
     
         18 . A method of alleviating or treating a lung defect in a mammal, the method comprising administering to the mammal a therapeutically effective amount of a composition comprising a population of lung cells produced by a method of differentiating a stem cell into a lung cell, thereby alleviating or treating said lung defect in said mammal, wherein the differentiation method comprise: a) inducing a stem cell into a definitive endoderm cell; b) inducing the definitive endoderm cell into an anterior foregut endoderm cell; c) inducing the anterior foregut endoderm cell into a lung cell, thereby differentiating a stem cell into a lung cell.