Entrapped stem cells and uses thereof

Abstract

The invention relates to the stem cells, embryonic stem cells in particular. It has been found that, when these stem cells are entrapped such that their proliferation is inhibited, they produce material which inhibits the proliferation of other, non-entrapped cells, including stem cells and neoplastic and/or hyperproliferative, but otherwise normal cells. It has also been found that entrapped cancer cells will produce material which inhibits the proliferation of stem cells. Further, it has been found that the entrapment of the stem cells inhibits their differentiation and thus the entrapment process can serve as a long-term storage device for maintaining the undifferentiated state of at least a portion of the entrapped cells.

1 . A composition of matter comprising a sample of stem cells entrapped in a biocompatible, selectively permeable structure, wherein entrapment of said sample of stem cells inhibits proliferation of at least a portion of the entrapped stem cells.  
     
     
         2 . The composition of matter of  claim 1 , wherein said stem cells are mammalian stem cells.  
     
     
         3 . The composition of matter of  claim 2 , wherein said mammalian stem cells are human stem cells.  
     
     
         4 . The composition of matter of  claim 2 , wherein said mammalian stem cells are murine stem cells.  
     
     
         5 . The composition of matter of  claim 1 , wherein said stem cells are embryonic stem cells.  
     
     
         6 . The composition of matter of  claim 1 , wherein said stem cells are entrapped in agarose.  
     
     
         7 . The composition of matter of  claim 6 , wherein said agarose is coated with agarose.  
     
     
         8 . The composition of matter of  claim 1 , wherein said stem cells are entrapped in a mixture of agarose and collagen, or a mixture of agarose and gelatin.  
     
     
         9 . The composition of matter of  claim 8 , wherein said mixture of agarose and collagen or said mixture of agarose and gelatin is coated with agarose.  
     
     
         10 . A process of inhibiting proliferation of at least a portion of a population of stem cells, comprising entrapping said stem cells in a biocompatible, selectively permeable structure which induces said stem cells to produce a factor which inhibits their proliferation.  
     
     
         11 . The process of  claim 10 , wherein said stem cells are mammalian stem cells.  
     
     
         12 . The process of  claim 11 , wherein said mammalian stem cells are human stem cells.  
     
     
         13 . The process of  claim 11 , wherein said mammalian cells are murine stem cells.  
     
     
         14 . The process of  claim 10 , wherein said stem cells are embryonic stem cells.  
     
     
         15 . The process of  claim 10 , wherein said stem cells are entrapped in agarose.  
     
     
         16 . The process of  claim 15 , wherein said agarose is coated with agarose.  
     
     
         17 . The process of  claim 10 , wherein said stem cells are entrapped in a mixture of agarose and collagen or a mixture of agarose and gelatin.  
     
     
         18 . The process of  claim 17 , which said mixture of agarose and collagen or mixture of agarose and gelatin is coated with agarose.  
     
     
         19 . A method for inhibiting proliferation of at least a portion of a non-entrapped cell population, comprising culturing said cell population in the presence of the composition of matter of  claim 1 .  
     
     
         20 . The method of  claim 19 , wherein said cell population is a stem cell population.  
     
     
         21 . The method of  claim 19 , wherein said cell population is from a species different from the species of origin of the cells entrapped in said composition of matter.  
     
     
         22 . The method of  claim 19 , wherein said cell population is from the same species as is the species of origin of the cells entrapped in said composition of matter.  
     
     
         23 . The method of  claim 19 , wherein said cell population is a cancer cell population.  
     
     
         24 . The method of  claim 19 , wherein said cell population is a mammalian cell population.  
     
     
         25 . The method of  claim 19 , wherein said cell population is a hyperproliferative cell population.  
     
     
         26 . The method of  claim 24 , wherein said mammalian cell population is a human cell population.  
     
     
         27 . The method of  claim 24 , wherein said mammalian cell population is a murine cell population.  
     
     
         28 . A method for inhibiting proliferation of at least a portion of a cell population comprising administering the composition of matter of  claim 1  to a subject in need thereof, in an amount sufficient and at a site sufficient to inhibit proliferation of at least a portion of said cell population.  
     
     
         29 . The method of  claim 28 , wherein said cell population is a stem cell population.  
     
     
         30 . The method of  claim 28 , wherein said cell population comprises neoplastic cells.  
     
     
         31 . The method of  claim 28 , wherein said cell population is a hyperproliferative cell population.  
     
     
         32 . The method of  claim 28 , wherein cells entrapped in said composition of matter are from a species different from said subject.  
     
     
         33 . The method of  claim 28 , wherein cells entrapped in said composition of matter are from the same species as said subject.  
     
     
         34 . The method of  claim 33 , wherein said cells are autologous to said subject.  
     
     
         35 . The method of  claim 28 , wherein said subject is a human.  
     
     
         36 . The method of  claim 33 , wherein said subject is a human.  
     
     
         37 . A method for inhibiting proliferation of a non-entrapped cell population, comprising culturing the composition of matter of  claim 1 , in a medium for a time sufficient to permit diffusion of a cell proliferation inhibiting material into said medium, and contacting said medium to said non-entrapped cell population for a time sufficient to inhibit proliferation of said non-entrapped cell population.  
     
     
         38 . The method of  claim 37 , wherein said non-entrapped cell population is a stem cell population.  
     
     
         39 . The method of  claim 37 , wherein said non-entrapped cell population and the cells entrapped in said composition of matter are from different species.  
     
     
         40 . The method of  claim 37 , wherein said non-entrapped cell population and the cells entrapped in said composition of matter are from the same species.  
     
     
         41 . The method of  claim 38 , wherein said stem cell population is a mammalian cell population.  
     
     
         42 . The method of  claim 41 , wherein said mammalian cell population is a human cell population.  
     
     
         43 . The method of  claim 41 , wherein said mammalian cell population is a murine cell population.  
     
     
         44 . The method of  claim 37 , comprising contacting said medium to a subject in need of inhibition of proliferation of a cell population.  
     
     
         45 . The method of  claim 44 , wherein said cell population is a stem cell population.  
     
     
         46 . The method of  claim 44 , wherein said cell population comprises neoplastic cells.  
     
     
         47 . The method of  claim 44 , wherein cells entrapped in said composition of matter are from a species different from said subject.  
     
     
         48 . The method of  claim 44 , wherein cells entrapped in said composition of matter are from the same species as said subject.  
     
     
         49 . The method of  claim 48 , wherein said cells are autologous to said subject.  
     
     
         50 . A method for inhibiting proliferation of a non-entrapped population of stem cells, comprising culturing said stem cells in the presence of a composition of matter which comprises a sample of cancer cells entrapped in a biocompatible, selectively permeable structure, wherein said sample of cancer cells produces material which inhibits proliferation of said stem cells.  
     
     
         51 . The method of  claim 50 , wherein said stem cells are mammalian stem cells.  
     
     
         52 . The method of  claim 50 , wherein said stem cells are embryonic stem cells.  
     
     
         53 . The method of  claim 50 , wherein said mammalian stem cells are human stem cells.  
     
     
         54 . The method of  claim 50 , wherein said mammalian stem cells are murine stem cells.  
     
     
         55 . The method of  claim 50 , wherein said stem cells and cancer cells originate from the same species.  
     
     
         56 . The method of  claim 50 , wherein said stem cells and cancer cells originate from different species.  
     
     
         57 . A method for inhibiting proliferation of non-entrapped stem cells, comprising culturing a composition of matter which comprises a sample of cancer cells entrapped in a biocompatible, selectively permeable structure, wherein said sample of cancer cells produces material which inhibits proliferation of stem cells and which diffuses into a culture medium, and contacting said culture medium to said stem cells.  
     
     
         58 . The method of  claim 57 , wherein said stem cells are mammalian stem cells.  
     
     
         59 . The method of  claim 57 , wherein said stem cells are embryonic stem cells.  
     
     
         60 . The method of  claim 58 , wherein said mammalian stem cells are human stem cells.  
     
     
         61 . The method of  claim 58 , wherein said mammalian stem cells are murine stem cells.  
     
     
         62 . The method of  claim 57 , wherein said stem cells and cancer cells originate from the same species.  
     
     
         63 . The method of  claim 57 , wherein said stem cells and cancer cells originate from different species.  
     
     
         64 . A composition of matter comprising a sample of stem cells entrapped in a biocompatible, selectively permeable structure, wherein entrapment of said sample of stem cells causes at least a portion of the entrapped stem cells to remain in an undifferentiated state.  
     
     
         65 . A process of inhibiting differentiation of at least a portion of a population of stem cells, comprising entrapping said stem cell in a biocompatible, selectively permeable structure which induces said stem cells to produce a factor which causes such portion to remain in an undifferentiated state.  
     
     
         66 . A method for inhibiting differentiation of at least a portion of a population of stem cells, comprising entrapping said stem cells in a biocompatible, selectively permeable structure, wherein such entrapment causes at least a portion of said stem cells to remain in an undifferentiated state.