Compositions and methods for lung regeneration

Abstract

Described herein are stein cells and related factors for treating degenerative and inflammatory disorders of lung tissue.

1 . A composition comprising a clonal population of airway epithelial stem cells, which cells are keratin 5 (Krt5) positive and p63 positive, can propagate for at least 20 doublings while maintaining a pluripotent phenotype, and can differentiate into airway epithelia. 
     
     
         2 . A composition of purified airway epithelial stem cells, which cells are keratin 5 (Krt5) positive and p63 positive, can propagate for at least 20 doublings while maintaining a pluripotent phenotype, and can differentiate into airway epithelia. 
     
     
         3 . The composition of  claim 1  wherein the airway epithelial stem cells are nasal epithelial stem cells (NESCs). 
     
     
         4 . The composition of  claim 1  wherein the airway epithelial stem cells are trachael airway stem cells (TASCs). 
     
     
         5 . The composition of  claim 1  wherein the airway epithelial stem cells are distal airway stem cell (DASC). 
     
     
         6 . The composition of  claim 1  wherein the airway epithelial stem cells are mammalian cells. 
     
     
         7 . The composition of  claim 1  wherein the airway stem epithelial cells are human cells. 
     
     
         8 . A composition comprising at least 10 5  distal airway stem cell (DASCs), which cells are keratin 5 (Krt5) positive and p63 positive, have mRNA levels for one or more, and preferably each of, PLUNC, SCGB3A1, GPX2, LTF, SCGB3A2, CYP2F2 and/or GABRP at least ten times greater than in normal differentiated alveoli cells, can propagate for at least 20 doublings while maintaining a pluripotent phenotype, and can differentiate into airway epithelia. 
     
     
         9 . Use of the composition of  claim 1  in the manufacture of a medicament for promoting lung tissue regeneration and/or preventing or slowing lung tissue degeneration. 
     
     
         10 - 17 . (canceled) 
     
     
         18 . A method of screening for an agent which may be used to cause lung regeneration, comprising
 a) providing airway epithelial stem cells, which cells are keratin 5 (Krt5) positive and p63 positive, can propagate for at least 50 doublings while maintaining a pluripotent phenotype, and can differentiate into airway epithelia.   b) contacting the airway epithelial stem cells with a test agent;   c) detecting the ability of the test agent to increase one or more of viability, growth, migration or differentiation of the airway epithelial stem cells, and/or increased secretion of paracrine factors able to prevent IL-13 mediated inflammation and/or remodeling of lung tissue;   
       wherein if the test agent increases viability, growth, migration, differentiation and/or paracrine secretion of the airway epithelial stem cells than the test agent may be effective in causing lung regeneration. 
     
     
         19 . The method of  claim 18 , wherein the airway epithelial stem cells are distal airway stem cell (DASC) isolated from isolated from distal airway tissue. 
     
     
         20 . The method of  claim 18 , wherein the airway epithelial stem cells are provided as a clonal population of cells. 
     
     
         21 . The method of  claim 18 , wherein the test agent is small molecule, carbohydrate, peptide or nucleic acid. 
     
     
         22 . The method of  claim 18 , wherein the test agent specifically binds to a cell surface protein on the clonal population of cells, such as the test agent being an antibody or antibody mimetic.