1999 Fiscal Year Final Research Report Summary
ALLOGENEIC MARROW CELLS/CERAMIC COMPOSITE TRANSPLANTATION WITH IMMUNOSUPPRESSANTS
| Project/Area Number |
09558121
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Biomedical engineering/Biological material science
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| Research Institution | Nara Medical University |
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Principal Investigator |
OHGUSHI Hajime NARA MEDICAL UNIV., ORTHOPEDICS, ASSISTANT PROFESSOR, 医学部, 講師 (80213669)
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| Co-Investigator(Kenkyū-buntansha) |
OHTA Tomohiro TEIJIN Co., RESEARCH INST.UTE OF BIOLOGY, PRINCIPLE INVESTIGATOR, 生物医学総合研究所, 主任研究員
YOSHIKAWA Takafumi NARA MEDICAL UNIV., PATHOLOGY, ASSISTANT PROFESSOR, 医学部, 講師 (90275347)
DOHI Yoshiko NARA MEDICAL UNIV., PUBLIC HEALTH, ASSOCIATE PROFESSOR, 医学部, 助教授 (50155628)
YOSHINARI Hiroki TEIKYO-UNIVERSITY, MATERIAL SCIENCE, ASSISTANT PROF., 理工学部, 助手 (80220698)
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| Project Period (FY) |
1997 – 1999
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| Keywords | bone marrow / immunosuppression / bone formation |
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| Research Abstract |
Porous hydroxyapatite (HA) ceramics were combined with either allogeneic (ACI) or isogeneic (Fischer 344) rat marrow cells and implanted in subcutaneous sites of Fischer rats. FK506 as an immunosuppressant or saline was administrated to the recipient rats. The implanted marrow/HA composites were harvested at day 28 and analyzed for bone forming capability by determining osteoblastic phenotype expression levels of protein synthesis and gene expression. The alkaline phosphatase (ALP) activity and osteocalcin contents were very low and mRNAs (Northern blot analysis) were not detected in the allografts without FK506. However, high activity of ALP and high content of osteocalcin were found and obvious mRNAs were detected in the allografts with FK506 and the isografts (with and without FK506). This analysis indicates the osteogenic potential of allogeneic marrow cells in the presence of FK506. The histological sections revealed that allografts without FK506 did not show bone formation but did show the infiltration of many small cells in the ceramics indicating an immunological reaction, however the allografts with FK506 and the isografts (with and without FK506) showed consistent de novo bone formation on the HA pore surface. These results indicate that FK506 can suppress the immunological reaction in the allografts and induce a condition to support osteoblastic defferentiation of allogeneic rat marrow stromal stem cells on the surface of HA ceramics. We also performed cultured allogeneic and isogenic marrow cells/HA composite transplantation and found that the allogeneic cultured marrow/HA composite did not show bone formation whereas the composites showed extensive bone formation with FK506 administration. Therefore, our study suggest the possible feasibility of clinical transplantation of allogeneic bone marrow for a selected bone graft in applications using adjuvant systemic immunosuppression.
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