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2002 Fiscal Year Final Research Report Summary

A study for the mechanism of negative hematopoietic regulation by bone marrow microenvironment.

Research Project

Project/Area Number 13670028
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General anatomy (including Histology/Embryology)
Research InstitutionNihon University

Principal Investigator

AIZAWA Shin  Nihon University School of Medicine, Professor, 医学部, 教授 (30202443)

Project Period (FY) 2001 – 2002
Keywordsbone marrow stromal cell / hematopoietic stem cell / apoptosis / cyclic polylactate / hematopoietic microenvironment / hematopoiesis / myelodysplastic syndrome / anaerobic glycolysis
Research Abstract

Normal hematopoiesis is characterized by a balanced interplay between hematopoietic stem cells and the cells and molecules that form the portion of the microenvironment in which blood cell production takes place. This in turn suggests that alterations in some of the elements of this microenvironment may result in abnormal production of blood cells. Bone marrow stromal cells, a heterogenous collection of mesenchymal cells that grow as an adherent layer in bone marrow culture, are an essential component of the microenvironment. In this study, the hematopoietic regulatory mechanisms of stromal cell were investigated in vitro.
1) A cloned stromal cell line (LS801) was established from an myelodysplastic syndrome (MDS) refractory anemia (RA) patient by introducing recombinant SV40-adenovirus vector containing the SV40 early gene. LS801 induced an apoptotic change in hematopoietic cells in a coculture system. When hematopoietic cells were cocultured but kept separate from LS801 by a 0.45μm Mi … More llipore membrane to prevent their attachment, the action of LS801 in inducing apoptosis of hematopoietic cells was inhibited. These findings suggest that LS801 induced an apoptotic change of hematopoietic cells by producing diffusible factor(s) and via direct cellular interactions.
2) A supramolecular oligomer, cyclic polylactate was isolated from the culture medium of LS801. This oligomer was found to induce apoptotic change in hematopoietic cells. The mechanism responsible for this action remains unclear, however, the activities of glycolytic enzymes of hematopoietic cells treated with this oligomer were suppressed.
3) In some stromal cells originated from MDS patients induced apoptotic change of hematopoietic cells by producing TNFα. We found that the treatment with vitamin K2 suppressed the production of TNFα from these stromal cells, and hematopoiesis in culture with these stromal cells were stimulated.
All these findings suggest that stromal cells possess both stimulatory and inhibitory action for the proliferation and differentiation of hematopoietic cells. Less

  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Nishi T., Aizawa S.et al.: "Spatial redox regulation of a critical cysteine residue of NF-kappa B in vivo"J Biol Chem. 277. 44548-44556 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kunieda M., Aizawa S., et al.: "Formation if lymph follicles and germinal centers in the somatic and mesenteric lymph nodes or growing mice during ontogenesis"Okajimas Folia Anat Jpn. 79. 63-74 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiramoto M., Aizawa S., et al.: "Factors in granulopoiesis produced by bone marrow stromal cells"Exp Hematol. 30. 77 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsuboi I., Aizawa S., et al.: "Age-related change in myelopoietic response to lipopolysaccharide in senescence-accelerated mice(SAM)"Exp Hematol. 30. 87 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Aikawa S., Aizawa S., et al.: "Requirement of soluble factors produced by bone marrow stromal cells on the growth of novel established human myeloma cell line"Int J Oncol. 22. 631-637 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Aizawa S., Kanno H., et al.: "Ineffective erythropoiesis in the spleen of a patient with pyruvate kinase deficiency"Am J Hematol. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiramoto M., Aizawa S., et al.: "Methods in Enzymology"Elsevier Science, USA. 8 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hoshi H., Horie K., Tanaka K., Nagata H., Aizawa S., Hiramoto M., Ryouke T., Aijima H.: "Patterns of age-dependent changes in the numbers of lymph follicles and germinal centers in somatic and mesenteric lymph nodes in growing C57B1/6 mice"J Anat.. 198. 189-205 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshimatsu T., Saitoh A., Ryu J., Shima D., Handa H., Hiramoto M., Kawakami Y., Aizawa S.: "Characterization of immortalized human chondrocytes originated from osteoarthritis cartilage"Int J Mol Med.. 8. 345-351 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsukawa Y., Aizawa S., Itoh T., Hatta Y., Nishinarita S., Horie T., Suzuki A., Takahashi S., Asano S., Mine T.: "Seroprevalence of helicobacter pylori after bone marrow transplantation"Int J Immunotherapy. 17. 21-24 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kunieda M., Hiramoto M., Horie K., Nagata H., Aizawa S., Hoshi H.: "Formation of lymph follicles and germinal centers in the somatic and mesenteric lymph nodes of growing mice during ontogenesis"Okajima Folia Anat Jpn.. 79. 63-74 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishi T., Shimizu N., Hiramoto M., Sato I., Yamaguchi Y., Hasegawa M., Aizawa S.. Tanaka H., Kataoka K., Watanabe H., Handa H.: "Spatial redox regulation of a critical cystein residue of NF-KB in vivo"J Biol Chem.. 277. 44548-44556 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Aikawa S., Hatta Y., Tanaka M., Kaneita Y., Yasukawa K., Sawada U., Horie T., Tsuboi I., Aizawa S.: "Requirement of soluble factors produced by bone marrow stromal cells on the growth of novel established human myeloma cell line"Int J Oncol.. 22. 631-637 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Aizawa S.. Kohdera U., Hiramoto M., Kawakami Y., Aisaki K., Kobayashi Y., Miwa S., Fujii H., Kanno H.: "Ineffective erythropoiesis in the spleen of a patient with pyruvate kinase deficiency"Am J Hematol.. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiramoto M, Shimizu N, Nishi T, Shima D, Aizawa S. Tanaka H, Hatakeyama M, Kawaguchi H, Handa H.: "High-performance affinity beads for identifying anti-NK-kB drug receptors"Methods in Enzymolozy, Elsevier Science. vol. 353. 81-88 (2002)

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      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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