Inhibitor of stem cell proliferation and uses thereof

Abstract

Disclosed and claimed are methods for the isolation and use of stem cell inhibiting factors for regulating the abnormal stem cell cycle and for accelerating the post-chemotherapy peripheral blood cell recovery. Also disclosed and claimed are the inhibitors of stem cell proliferation.

What is claimed is:  
     
         1 . A pharmaceutical composition comprising the alpha chain of hemoglobin in a pharmaceutically acceptible carrier.  
     
     
         2 . A pharmaceutical composition comprising the beta chain of hemoglobin in a pharmaceutically acceptible carrier.  
     
     
         3 . A pharmaceutical composition as in  claim 1  further comprising the beta chain of hemoglobin.  
     
     
         4 . A pharmaceutical composition as in claim  1 - 3  in unit dosage form.  
     
     
         5 . A pharmaceutical composition as in  claim 4  comprising 0.1 mgs. to 6 gms. of the alpha and/or beta chain of hemoglobin.  
     
     
         6 . A method of inhibiting stem cell proliferation comprising contacting hematopoietic cells with a stem cell proliferation inhibiting amount of INPROL.  
     
     
         7 . A method as in  claim 6  wherein said INPROL is selected from the group consisting of the alpha chain of hemoglobin and the beta chain of hemoglobin.  
     
     
         8 . A method of stimulating the growth of B cells which comprises contacting hematopoietic cells with a growth stimulating amount of INPROL.  
     
     
         9 . A method of treating cancer in a mammal suffering therefrom comprising the steps of: 
 a) administering radiotherapy or chemotherapy, and    b) administering a stem cell proliferation inhibiting amount of INPROL    
     
     
         10 . A method as in  claim 9  wherein steps a and b are repeated one or more times.  
     
     
         11 . A method as in  claim 9  wherein step a is conducted after step b.  
     
     
         12 . A method as in  claim 9  wherein step b is conducted within 24 hours before or after step a.  
     
     
         13 . A method for treating cancer in a mammal comprising: 
 a) removing bone marrow from said mammal,    b) treating said bone marrow ex vivo with INPROL,    c) treating said bone marrow of step b with chemotherapy or radiation,    d) performing myeloablative treatment on said mammal, and    e) transplanting into said mammal the bone marrow of step c.    
     
     
         14 . A method as in  claim 13  wherein said cancer is leukemia.  
     
     
         15 . A method of inhibiting stem cell division in a mammal exposed to an agent which damages or destroys stem cells undergoing division comprising administering a stem cell proliferation inhibiting amount of INPROL.  
     
     
         16 . A method as in  claim 15  wherein said agent is an antiviral agent.  
     
     
         17 . A method of maintaining mammalian hematopoietic stem cells ex vivo comprising contacting hematopoietic cells with a stem cell proliferation inhibiting amount of INPROL.  
     
     
         18 . A method as in  claim 17  wherein said hematopoietic cells are selected from the group consisting of bone marrow cells, peripheral blood cells and cord blood cells.  
     
     
         19 . A method of treating a myeloproliferative or autoimmune disease or epithelial stem cell hyperproliferation in a mammal suffering therefrom comprising administering a hyperproliferative reducing amount of INPROL.  
     
     
         20 . A method as in  claim 19  wherein said myeloproliferative disease is a myelodysplastic syndrome.  
     
     
         21 . A method for differentially protecting normal stem cells and not cancer cells in a mammal from chemotherapy or radiation comprising administering a stem cell protecting amount of INPROL.  
     
     
         22 . A method as in  claim 21  wherein said INPROL is administered after said normal stem cells are induced to proliferate by exposure to a cytotoxic drug or radiation.  
     
     
         23 . A method of vaccinating a mammal comprising administering INPROL as an adjuvant before, during or after administration of a vaccine.  
     
     
         24 . A method of purifying an inhibitor of stem cell proliferation substantially free from other proteinaceous material comprising the following steps: 
 a) isolating bone marrow and removing particulate matter from an extract;    b) heating said extract and removing precipitate;    c) acid precipitating said extract and collecting precipitate; and    d) isolating said inhibitor by reverse pahse chromatography.    
     
     
         25 . A purified inhibitor of stem cell proliferation wherein said inhibitor is purified to apparent homogeneity by the method of  claim 24 .  
     
     
         26 . A method of treating a mammal having immunodepression caused by stem cell hyperproliferation comprising administering to said mammal an hyperproliferation reversing amount of INPROL.