1998 Fiscal Year Final Research Report Summary
CHARACTERIZATION OF PURIFIED HUMAN HEMATOPOIETIC PROGENITOR CELLS OF BONE MARROW AND THEIR RECONSTITUTING ABILITY IN GENOGENEIC TRANSPLANTATION
| Project/Area Number |
09670809
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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 | HIROSHIMA UNIVERSITY |
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Principal Investigator |
KOBAYASHI Masao FACULTY OF EDUCATION,CHILD HEALTH,HIROSHIMA UNIVERSITY PROFESSOR, 教育学部, 教授 (00162016)
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| Co-Investigator(Kenkyū-buntansha) |
KATOH Osamu RESEARCH INSTITUTE FOR RADIATION BIOLOGY AND MEDICINE,ENVIRONMENT AND MUTATIONS,, 原爆放射能医学研究所, 助教授 (90214361)
FUJITA Naoto UNIVERSITY HOSPITAL,PEDIATRICS,RESEARCH ASSOCIATE, 医学部・附属病院, 助手 (60274081)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Hematopoietic progenitors / Hematopoietic factors / Cell sorting / Xenogeneic transplantation / Severe congenital neutropenia |
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| Research Abstract |
We have tested the effects of early-acting hematopoietic factors on the proliferation of primitive human bone marrow progenitor cells in serum-deprived culture, and the engrafting capability of purified primitive human bone marrow cells using the NOD/SCID/human xenograft model. Primitive human bone marrow cells were purified by setting the FAGS Vantage based on the expression of CD34, Kit receptor and CD38. The results of single-cell culture system suggest that steel factor (SF), the ligand for flk2/flt3 (FL) and thrombopoietin (TPO) play important roles in survival and proliferation of primitive human hematopoietic progenitors.
The engrafting capabilities of the primitive bone marrow cells were examined by injecting them into NOD/SCID mice. As marker for engraftment, we analyzed CD45-positive cells and human specific DNA using PCR The day-90 engraftment in the bone marrow was seen with fresh cells (CD34^+/Kit^+) but not with cells cultured in the presence of SF, FL and TPO.To evaluate the engrafting capability of cultured cells, the development of culture system using the combination of hematopoietic factors might be required.
We studied the responsiveness of primitive myeloid progenitor cells to hematopoietic factors in four patients with SCN.The number of granulocyte-macrophage (GM) colonies formed in patients was decreased in response to granulocyte colony-stimulating factor (G-CSF) in both serum-supplemented and serum-deprived culture. The results suggest that primitive myeloid progenitor cells of patients with SCN have defective responsiveness to not only G-CSF but also the early- or intermediate-acting hematopoietic factors, SF, FL, and IL-3.
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