Tumor suppression using placental stem cells

Abstract

The present invention provides methods of suppression of tumor cell proliferation and tumor growth using placental stem cells and placental stem cell populations. The invention also provides methods of producing and selecting placental cells and cell populations on the basis of tumor suppression, and compositions comprising such cells and cell populations.

1 . A method of suppressing the proliferation of a plurality of tumor cells comprising contacting said plurality of tumor cells with a plurality of placental stem cells for a time sufficient for said placental stem cells to detectably suppress proliferation of said plurality of tumor cells, as compared to a plurality of said tumor cells not contacted with placental stem cells. 
     
     
         2 . The method of  claim 1 , wherein said placental stem cells:
 express CD200 and HLA-G,   express CD73, CD105, and CD200,   express CD200 and OCT-4,   express CD73, CD105, and HLA-G,   express CD73 and CD105, and facilitate the formation of one or more embryoid-like bodies in a population of placental cells that comprise the stem cell, when said population is cultured under conditions that allow formation of embryoid-like bodies, and/or   express OCT-4 and facilitate the formation of one or more embryoid-like bodies in a population of placental cells that comprise the stem cell, when said population is cultured under conditions that allow formation of embryoid-like bodies.   
     
     
         3 . The method of  claim 1 , wherein said tumor cells are part of a solid tumor. 
     
     
         4 . The method of  claim 1 , wherein said plurality of tumor cells are histiocytic lymphoma cells, chronic myelogenous leukemia cells, acute T-cell leukemia cells, acute myelogenous leukemia cells, colon adenocarcinoma cells, retinoblastoma cells or lung carcinoma cells. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein said contacting is performed in vivo. 
     
     
         7 . The method of  claim 6 , wherein said contacting is performed in an individual who comprises said tumor cells. 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein at least a portion of said placental stem cells have been engineered to express a cytokine. 
     
     
         13 . The method of  claim 12 , wherein said cytokine is IFN-β or IL-2. 
     
     
         14 . The method of  claim 1 , additionally comprising contacting said tumor cells with one or more anticancer compounds. 
     
     
         15 . The method of  claim 1 , comprising contacting said tumor cells with a plurality of mesenchymal stem cells. 
     
     
         16 . The method of  claim 15 , wherein said mesenchymal stem cells are bone marrow-derived mesenchymal stem cells. 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . The method of  claim 1 , wherein said placental stem cells suppress said tumor cell proliferation by at least 50% compared to proliferation of an equivalent number of tumor cells in the absence of said placental stem cells. 
     
     
         23 . The method of  claim 1 , wherein said placental stem cells suppress said tumor cell proliferation by at least 75% compared to proliferation of an equivalent number of tumor cells in the absence of said placental stem cells. 
     
     
         24 . The method of  claim 7 , comprising determining that said placental stem cells detectably suppress the proliferation of tumor cells prior to said contacting. 
     
     
         25 . The method of  claim 24 , wherein said sample tumor cells are tumor cells of the same tissue origin as said tumor cells contacted with said placental stem cells. 
     
     
         26 . The method of  claim 25 , wherein said sample tumor cells are tumor cells of an individual. 
     
     
         27 . The method of  claim 24 , wherein said determining comprises determining that said sample tumor cells are detectably suppressed by direct contact with said placental stem cells. 
     
     
         28 . The method of  claim 24 , wherein said determining comprises determining that said sample tumor cells are detectably suppressed by said placental stem cells without direct contact between said placental stem cells and said sample tumor cells. 
     
     
         29 . A method of producing a population of placental stem cells, comprising selecting placental stem cells that
 (a) adhere to a substrate, and   (b) express CD200 and HLA-G, or
 express CD73, CD105, and CD200, or 
 express CD200 and OCT-4, or 
 express CD73, CD105, and HLA-G, or 
 express CD73 and CD 105, and facilitate the formation of one or more embryoid-like bodies in a population of placental cells that comprise the stem cell, when said population is cultured under conditions that allow formation of embryoid-like bodies, or 
 express OCT-4, and facilitate the formation of one or more embryoid-like bodies in a population of placental cells that comprise the stem cell, when said population is cultured under conditions that allow formation of embryoid-like bodies; and 
   determining that said placental stem cells detectably suppress tumor cell proliferation, wherein said tumor cells are histiocytic lymphoma cells, chronic myelogenous leukemia cells, acute T-cell leukemia cells, acute myelogenous leukemia cells, colon adenocarcinoma cells, retinoblastoma cells or lung carcinoma cells; and   and isolating said placental stem cells from other cells to form a cell population.   
     
     
         30 . An isolated cell population comprising placental stem cells, wherein said placental stem cells:
 (a) adhere to a substrate,   (b) express CD200 and HLA-G, or
 express CD73, CD105, and CD200, or 
 express CD200 and OCT-4, or 
 express CD73, CD 105, and HLA-G, or 
 express CD73 and CD 105, and facilitate the formation of one or more embryoid-like bodies in a population of placental cells that comprise the placental stem cells, when said population is cultured under conditions that allow formation of embryoid-like bodies, or 
 express OCT-4 and facilitate the formation of one or more embryoid-like bodies in a population of placental cells that comprise the placental stem cells, when said population is cultured under conditions that allow formation of embryoid-like bodies; and 
   (c) have been determined to detectably suppress proliferation of said plurality of tumor cells, as compared to a plurality of tumor cells not contacted with placental stem cells.   
     
     
         31 . (canceled)