Inhibitor and stimulator of stem cell proliferation and uses thereof

Abstract

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

1 - 45 . (canceled)  
     
     
         46 . A peptide having the sequence selected from the group consisting of biotin-Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val (SEQ ID NO:36), (iodo)Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val (SEQ ID NO:37), Phe-Pro-His-(iodo)Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val (SEQ ID NO:38), and (iodo)Phe-Pro-His-(iodo)Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val (SEQ ID NO:39).  
     
     
         47 - 68 . (canceled)  
     
     
         69 . A method of maintaining mammalian hematopoietic stem cells ex vivo comprising contacting hematopoietic cells with a stem cell proliferation stimulating amount of INPROL and/or an opiate compound.  
     
     
         70 . A method as in  claim 69  wherein said hematopoietic cells are selected from the group consisting of bone marrow cells, peripheral blood cells, mobilized peripheral blood cells, fetal liver, and umbilical cord blood cells.  
     
     
         71 . A method as in  claim 69  wherein said opiate compound is selected from the group consisting of morphine, etorphine, codeine, heroin, hydromorphone, oxymorphone, levorphanol, levallorphan, codeine, hydrocodone, oxycodone, nalorphine, naloxone, naltrexone, buprenorphine, butanorphanol, nalbuphine, meperidine, alphaprodine, diphenoxylate, fentanyl, (D-Ala2,N-Me-Phe4,glycinol5)-Enkephalin, (D-Arg2,Lys4)-Dermorphin-(1-4)-amide, and nociceptin.  
     
     
         72 . A method of treating a myeloproliferative disease, hematopoieitic or epithelial stem cell hypoproliferation in a mammal suffering therefrom comprising administering a stimulatory amount of INPROL and/or an opiate compound.  
     
     
         73 . A method as in  claim 72  wherein said myeloproliferative disease is a myelodysplastic syndrome or aplastic anemia.  
     
     
         74 . A method as in  claim 72  wherein said opiate compound is selected from the group consisting of morphine, etorphine, codeine, heroin, hydromorphone, oxymorphone, levorphanol, levallorphan, codeine, hydrocodone, oxycodone, nalorphine, naloxone, naltrexone, buprenorphine, butanorphanol, nalbuphine, meperidine, alphaprodine, diphenoxylate, fentanyl, (D-Ala2,N-Me-Phe4,glycinol5)-Enkephalin, (D-Arg2,Lys4)-Dermorphin-(1-4)-amide, and nociceptin.  
     
     
         75 . A method for treating or preventing stem cell exhaustion comprising administering a stem cell proliferation inhibitory amount of INPROL and/or an opiate compound.  
     
     
         76 . A method as in  claim 75  wherein said stem cell exhaustion is due to an acquired immune deficiency syndrome.  
     
     
         77 . A method as in  claim 75  wherein said opiate compound is selected from the group consisting of morphine, etorphine, codeine, heroin, hydromorphone, oxymorphone, levorphanol, levallorphan, codeine, hydrocodone, oxycodone, nalorphine, naloxone, naltrexone, buprenorphine, butanorphanol, nalbuphine, meperidine, alphaprodine, diphenoxylate, fentanyl, (D-Ala2,N-Me-Phe4,glycinol5)-Enkephalin, (D-Arg2,Lys4)-Dermorphin-(1-4)-amide, and nociceptin.  
     
     
         78 - 81 . (canceled)  
     
     
         82 . A method for conducting ex vivo stem cell expansion comprising contacting hematopoietic cells with a stem cell stimulatory amount of INPROL and/or an opiate compound.  
     
     
         83 - 88 . (canceled)  
     
     
         89 . A method of treating immune deficiency in a mammal comprising administering to said mammal an immunostimulatory amount of INPROL.  
     
     
         90 . A method as in  claim 89  wherein said INPROL is selected from the group consisting of the alpha chain of hemoglobin, the beta chain of hemoglobin, the gamma chain of hemoglobin, the delta chain of hemoglobin, the epsilon chain of hemoglobin, the zeta chain of hemoglobin, 
 a polypeptide having the sequence of amino acids 1-97 of the human alpha hemoglobin chain,    a polypeptide having the sequence of amino acids 1-94 of the human alpha hemoglobin chain,    Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val (SEQ ID NO:1),    Cys-Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala-Gln-Val-Cys (SEQ ID NO:2), and    Asp-Ala-Leu-Thr-Asn-Ala-Val-Ala-His-Val-Asp-Asp-Met-Pro-Asn-Ala-Leu-Ser-Ala (SEQ ID NO:3).    
     
     
         91 - 97 . (canceled)