Hemoglobin alpha chain peptide fragments useful for inhibiting stem cell proliferation

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.

1 . A method for conducting ex vivo expansion of hematopoietic stem cells in a cell population comprising contacting said cell population comprising hematopoietic stem cells with INPROL (inhibitor of stem cell proliferation) and at least one stimulatory cytokine, wherein said INPROL is selected from the group consisting of alpha-chain of hemoglobin, beta-chain of hemoglobin, gamma-chain of hemoglobin, delta-chain of hemoglobin, epsilon-chain of hemoglobin, zeta-chain of hemoglobin, a peptide consisting of the amino acid sequence of SEQ ID NO:1, a peptide consisting of the amino acid sequence of SEQ ID NO:2, a peptide consisting of the amino acid sequence of SEQ ID NO:3, a peptide consisting of the amino acid sequence of SEQ ID NO:4, a peptide consisting of the amino acid sequence of SEQ ID NO:5, a peptide consisting of the amino acid sequence of SEQ ID NO:6, a peptide consisting of the amino acid sequence of SEQ ID NO:7, a peptide consisting of the amino acid sequence of SEQ ID NO:8, a peptide consisting of the amino acid sequence of SEQ ID NO:9, a peptide consisting of the amino acid sequence of SEQ ID NO:10, a peptide consisting of the amino acid sequence of SEQ ID NO:11, a peptide consisting of the amino acid sequence of SEQ ID NO:12, a peptide consisting of the amino acid sequence of SEQ ID NO:13, and a peptide consisting of the amino acid sequence of SEQ ID NO:14; thereby expanding ex vivo hematopoietic stem cells in said cell population. 
     
     
         2 . The method of  claim 1  wherein said hematopoietic stem cells are cells selected from the group consisting of bone marrow cells, umbilical cord cells and peripheral blood cells. 
     
     
         3 . The method of  claim 1 , wherein said hematopoietic stem cells are mobilized peripheral blood cells. 
     
     
         4 . The method of  claim 1 , wherein said stimulatory cytokine is selected from the group consisting of IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-11, IL-12, IL-13, IL-14, G-CSF, GM-CSF, M-CSF, erythropoietin, megakaryocyte-CSF, stem cell factor, and thrombopoietin. 
     
     
         5 . A method for ex vivo culture of a cell population comprising contacting cells of said cell population comprised of hematopoietic stem cells with INPROL (inhibitor of stem cell proliferation) and at least one stimulatory cytokine in ex vivo culture, wherein said INPROL, is selected from the group consisting of alpha-chain of hemoglobin, beta-chain of hemoglobin, gamma-chain of hemoglobin, delta-chain of hemoglobin, epsilon-chain of hemoglobin, zeta-chain of hemoglobin, a peptide consisting of the amino acid sequence of SEQ ID NO:1, a peptide consisting of the amino acid sequence of SEQ ID NO:2, a peptide consisting of the amino acid sequence of SEQ ID NO:3, a peptide consisting of the amino acid sequence of SEQ ID NO:4, a peptide consisting of the amino acid sequence of SEQ ID NO:5, a peptide consisting of the amino acid sequence of SEQ ID NO:6, a peptide consisting of the amino acid sequence of SEQ ID NO:7, a peptide consisting of the amino acid sequence of SEQ ID NO:8, a peptide consisting of the amino acid sequence of SEQ ID NO:9, a peptide consisting of the amino acid sequence of SEQ ID NO:10, a peptide consisting of the amino acid sequence of SEQ ID NO:111, a peptide consisting of the amino acid sequence of SEQ ID NO:12, a peptide consisting of the amino acid sequence of SEQ ID NO:13, and a peptide consisting of the amino acid sequence of SEQ ID NO:14.