1989 Fiscal Year Final Research Report Summary
Bone marrow failure-Functional role of Bone marrow stromal cells.
| Project/Area Number |
63570168
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | KEIO UNIVERSITY |
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Principal Investigator |
WATANABE Yonosuke Department of Pathology, School of Medicine Keio University, Professor, 医学部・病理学, 教授 (20051013)
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| Co-Investigator(Kenkyū-buntansha) |
UMEZAWA Akihiro Department of Pathology, School of Medicine Keio University, Assistant, 医学部・病理学, 助手 (70213486)
AKASAKA Yoshikiyo Department of Pathology, School of Medicine Keio University, Assistant, 医学部・病理学, 助手 (60202511)
YAMAZAKI Kazuto Department of Pathology, School of Medicine Keio University, Assistant, 医学部・病理学, 助手 (40166640)
KURAMOCHI Shigeru Department of Pathology, School of Medicine Keio University, Assistant, 医学部・病理学, 助手 (70137991)
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| Project Period (FY) |
1988 – 1989
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| Keywords | bone marrow / stromal cell / electron microscope / gap junction / hematopoietic stem cells / monoclonal antibody / extracellular matrix / growth factor |
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| Research Abstract |
Abnormalities in hematopoietic microenvironment induce the poor hematopoiesis. These are based on the clinical analysis of aplastic anemia and experimental model of S1/S1^d anemic mice. The present studies were carried out to see the structure and function of marrow stromal cells in hematopoietic microenvironment at the molecular level.
Marrow stroma or adventitial and reticular cells were connected with each other by gap junctions. Stroma of S1/S1^d mice do have much gap junctional apparatus than W/W^v anemic mice and control mice. In the marrow stroma, new cell apparatus such as cilia and crystalloid inclusion were found. Marrow stromal cell line, H-1/A expressed heart muscle type gap junctional protein (Cx.43) constitutively as well as colony stimulating factor-1. Gap junctional communication and the expression of Cx.43 decrease during the adipocyte differentiation of H-1/A.
We obtained the monoclonal antibody R4A9D9 which recognized hematopoiesis-associated antigen. While the R4A9D9 antigen is expressed in only marrow stroma and spleen in adult mice, the antigen was detected in the fetal liver and choroid plexus where hematopoiesis was observed during the fetal period. The antigen was also induced in the lymph nodes by the irradiation. Functionally R4A9D9 antibody inhibited the spleen colony formation.
We isolated several new stromal cell line. BE-1, -2 and -3 cells were marrow endothel origin. These cells had ability of adhering to hematopoietic stem cells, i.e., CFU-c. The ability in the BE cells was enhanced by the exposure of interferon-gamma and interleukin-beta, and inhibited by heparitinase but not chondroitinase-ABC and hyaluronidase.
In the future, we will identify the membrane molecule of stromal cells which is critical for hematopoiesis, based on our morphological and biochemical results.
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