US2009214483A1PendingUtilityA1

Progenitor Cells and Uses Thereof

38
Individually held — no corporate assignee on recordPriority: Jun 30, 2005Filed: Jun 30, 2006Published: Aug 27, 2009
Est. expiryJun 30, 2025(expired)· nominal 20-yr term from priority
Inventors:Robert A. WeinbergSendurai A. ManiMai-Jing Liao
A61P 3/10A61P 7/00A61P 9/10A61P 9/00A61P 25/28A61P 25/00A61P 25/16A61P 29/00C12N 2501/15C12N 2501/60C12N 2510/00C12N 5/0631A61P 17/02A61P 19/02
38
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Claims

Abstract

Methods for preparing progenitor cells are described where epithelial cells are induced to undergo epithelial-mesenchymal transition as a result of exposure to an inducing agent or introduction of a gene therein that induces epithelial-mesenchymal transition. Progenitor cells resulting therefrom have use in cell-based therapies, among other utilities.

Claims

exact text as granted — not AI-modified
1 . A method for preparing isolated progenitor cells from epithelial cells comprising the steps of
 a. obtaining a population of epithelial cells;   b. inducing epithelial-mesenchymal transition (EMT) in the population of epithelial cells, whereby progenitor cells are generated in the population; and   c. isolating progenitor cells from the population after inducing EMT.   
   
   
       2 . The method of  claim 1  wherein said inducing comprises exposing the population of epithelial cells to an agent that induces epithelial-mesenchymal transition. 
   
   
       3 . The method of  claim 2  wherein said agent is TGF-β1, FGF-1, EGF, HGF/SF, BFGF, or PDGF. 
   
   
       4 . The method of  claim 1  wherein said inducing comprises introducing into the population of epithelial cells at least one gene encoding a protein that induces epithelial-mesenchymal transition. 
   
   
       5 . The method of  claim 4  wherein said gene is a transcription factor. 
   
   
       6 . The method of  claim 5  wherein the transcription factor is Snail, Twist, Slug, SIP1, FOXC1, FOXC2, Goosecoid, E47, or a functional variant thereof. 
   
   
       7 . The method of  claim 1  wherein said inducing comprises the steps of
 a. introducing into the epithelial cells an inducible gene encoding a protein that induces epithelial-mesenchymal transition, and   b. exposing the epithelial cells to an inducer of the expression of the gene.   
   
   
       8 . The method of  claim 7  wherein said gene encodes a transcription factor. 
   
   
       9 . (canceled) 
   
   
       10 . The method of  claim 7  wherein the inducible gene encodes a fusion polypeptide comprising the hormone-binding domain of the estrogen receptor. 
   
   
       11 . (canceled) 
   
   
       12 . The method of  claim 1  wherein the progenitor cells are CD44 high  and CD24 low . 
   
   
       13 - 15 . (canceled) 
   
   
       16 . A method for inducing the differentiation of progenitor cells comprising the steps of
 a. generating progenitor cells in accordance with  claim 7 ; and   b. withdrawing the inducer.   
   
   
       17 . (canceled) 
   
   
       18 . Isolated progenitor cells prepared by the process of  claim 1 . 
   
   
       19 . The isolated progenitor cells of  claim 18  wherein said inducing comprises exposing the epithelial cells to an agent that induces epithelial-mesenchymal transition. 
   
   
       20 . The isolated progenitor cells of  claim 19  wherein said agent is TGF-β1, FGF-1, EGF, HGF/SF, BFGF, or PDGF. 
   
   
       21 . The isolated progenitor cells of  claim 18  wherein said inducing comprises introducing into the population of epithelial cells a gene encoding a protein that induces epithelial-mesenchymal transition. 
   
   
       22 . The isolated progenitor cells of  claim 21  wherein the gene is a transcription factor. 
   
   
       23 . (canceled) 
   
   
       24 . The isolated progenitor cells of  claim 18  wherein said inducing comprises the steps of
 a. introducing into the epithelial cells an inducible gene encoding a protein that induces epithelial-mesenchymal transition, and   b. exposing the epithelial cells to an inducer.   
   
   
       25 . The isolated progenitor cells of  claim 24  wherein the gene is a transcription factor. 
   
   
       26 . (canceled) 
   
   
       27 . The isolated progenitor cells of  claim 24  wherein the inducible gene encodes a fusion polypeptide comprising the hormone-binding domain of the estrogen receptor. 
   
   
       28 - 31 . (canceled) 
   
   
       32 . Modified epithelial cells comprising an inducible gene encoding a protein that induces epithelial-mesenchymal transition when the cells are exposed to an inducer. 
   
   
       33 . The epithelial cells of  claim 32  wherein the gene is a transcription factor. 
   
   
       34 - 35 . (canceled) 
   
   
       36 . Modified progenitor cells comprising a vector comprising a gene encoding a protein that induces epithelial-mesenchymal transition. 
   
   
       37 . The progenitor cells of  claim 36  wherein the gene is on a vector under the control of a constitutive promoter. 
   
   
       38 . The progenitor cells of  claim 37  wherein said gene encodes a transcription factor. 
   
   
       39 - 43 . (canceled) 
   
   
       44 . Modified progenitor cells comprising an inducible gene encoding a protein that induces epithelial-mesenchymal transition. 
   
   
       45 . The progenitor cells of  claim 44  wherein the gene is a transcription factor. 
   
   
       46 . The progenitor cells of  claim 45  wherein the transcription factor is Snail Twist Slug, SIP1, FOXC1, FOXC2, Goosecoid, E47, or a functional variant thereof. 
   
   
       47 . The progenitor cells of  claim 46  wherein the inducible gene encodes a fusion polypeptide comprising the hormone-binding domain of the estrogen receptor. 
   
   
       48 - 53 . (canceled) 
   
   
       54 . A method for administering cell therapy to a mammalian subject comprising transplanting into the subject progenitor cells prepared by the method of
 a. obtaining a population of epithelial cells,   b. inducing epithelial-mesenchymal transition in the population of epithelial cells, whereby progenitor cells are generated in the population, and   c. transplanting the progenitor cells into the subject.   
   
   
       55 . A method for administering cell therapy to a mammalian subject comprising transplanting into the subject isolated progenitor cells prepared by the method of obtaining a population of isolated progenitor cells in accordance with  claim 1 ; and transplanting the isolated progenitor cells into the subject. 
   
   
       56 - 76 . (canceled) 
   
   
       77 . A method for identifying a progenitor cell in a cellular population comprising the step of detecting the expression of FOXC2 in the progenitor cell. 
   
   
       78 . (canceled) 
   
   
       79 . The method of  claim 1 , further comprising the step of differentiating the isolated progenitor cells in vitro. 
   
   
       80 . The method of  claim 79 , further comprising transplanting the differentiated progenitor cells into a mammalian subject. 
   
   
       81 . A composition comprising the modified progenitor cells of  claim 44  and an inducer.

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