2002 Fiscal Year Final Research Report Summary
A study on release from HIA restriction in cord blood stem cell transplantation
| Project/Area Number |
11670789
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | The Jikei University of Medicine |
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Principal Investigator |
HOSHI Y Jikei Univ., Dept. of transfusional medicine, 医学部, 教授 (20057011)
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| Co-Investigator(Kenkyū-buntansha) |
YANAGISAWA T Jikei Univ., Dept. of Pedatrics Research Assistant, 医学部, 助手 (40333091)
YUZA Y Jikei Univ., Dept. of Pedatrics Research Assistant, 医学部, 助手 (30277090)
UCHIYAMA H Jikei Univ., Dept. of Pedatrics assi prof, 医学部, 講師 (10168718)
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| Project Period (FY) |
1999 – 2002
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| Keywords | adhesion molecules / hematopoietic stem cell |
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| Research Abstract |
The objective of this study is to expand cord blood stem cells in vitro and simultaneously prepare an in vitro thymus-like environment to educate and induce immunotolerant cells that recognize grafts as self by blocking various adhesion molecules. Realization of this method widens the indicationof allograft of stem cells to all patients without KLA restriction as well as allows very useful ideal therapeutic strategy that completely eliminates burdens on donors. Using polyvinyl group-bound heparin developed byus (PV-heparin) , we attempted to develop an artificial bone marrow environment. PV-heparin is reproduction of the in vivo form of heparan sulfate, and its effect on hematopoietic stem cell growth may reflect the in vivo state. First, using plates coated with heparan sulfate, hematopoietic stemcells were pre-cultured with and without various cytokines and the numbersof hematopoietic stem cells were compared by colony assay. As a result, heparan sulfate did not promote various cytok
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ine-induced growth of hematopoietic step cells. When plates were coated with collagen, laminin, and fibronectin, which comprise the bone marrow environment as heparan sulfate, andthe ability of amplifying hematopoietic stem cells was investigated, no amplification was obtained. These findings suggested that heparan sulfate isnot useful for preparation of the pseudo-thyxnus environment.
In addition, we investigated the roles of adhesion molecules in preparation of bone marrow-like and thymus-like environments by comparison of the expression of various adhesion molecules in bone marrow, peripheral blood, and cord blood stem cells and investigation of the characteristics of each stem cells. The expression of CD49d was lower and the expression of SLeX was higher in peripheral blood CD34-positive cells. Since differentiation of peripheral blood stem cells is more advanced than cord blood stem cells,involvement of SLeX in differentiation of stem cells at the immature step was suggested. It may be rjiecessary to conduct studies of ligands and extracellular matrices involved in the expression of SLeX. Less
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