| Efficacy of transient treatment with FK506 in the early phase on cyclophosphamide-induced bone marrow chimerism and transplant tolerance across MHC barriers. | |
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MedLine Citation:
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PMID: 16376943 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The use of mixed allogeneic bone marrow chimerism to induce donor-specific transplantation tolerance has been extensively demonstrated. In the present study, we assessed the effect of combined use of a short course of FK506 and a single-dose cyclophosphamide (CYP) on the induction of tolerance and development of GVHD after allogeneic BMT. MATERIALS AND METHODS: Lewis rat (RT1(l)) recipients received BMT from Brown Norway (RT1(n)) donors on the next day after injection of CYP at a dose of 200 mg/kg. The recipients were further treated with no FK506 (n = 8), 0.3 mg/kg/day FK506 on days 10-16 (n = 6), or the same dose of FK506 on days 0-6 (n = 6). In a subgroup of animals, heterotopic heart transplantation was performed to investigate transplantation tolerance. RESULTS: Six of eight recipient rats that did not receive FK506 died of severe GVHD, while high levels of chimerism were induced. Recipients of FK506 in the later phase developed mild transient GVHD around 2 to 3 weeks after BMT and recovered thereafter; however, the level of chimerism was significantly decreased (2.8 +/- 2.3% on day 100). Treatment with FK506 in the early phase completely prevented the development of GVHD and induced stable allogeneic chimerism in the long-term (13.8 +/- 8.3% on day 100). These recipients with stable chimerism accepted subsequent BN heart allografts indefinitely (>200 days x 5), while rejecting third-party (BUF) heart allografts by day 12. CONCLUSIONS: Early transient FK506 promotes the induction of stable bone marrow chimerism without GVHD after BMT with CYP pretreatment. The timing of treatment with FK506 is critical with a view to preventing GVHD and inducing stable long-lasting chimerism. |
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Authors:
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Junji Okayama; Saiho Ko; Hiromichi Kanehiro; Hideki Kanokogi; Yoshiyuki Nakajima |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-12-27 |
Journal Detail:
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Title: The Journal of surgical research Volume: 133 ISSN: 0022-4804 ISO Abbreviation: J. Surg. Res. Publication Date: 2006 Jun |
Date Detail:
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Created Date: 2006-05-29 Completed Date: 2006-07-06 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0376340 Medline TA: J Surg Res Country: United States |
Other Details:
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Languages: eng Pagination: 61-8 Citation Subset: IM |
Affiliation:
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Department of Surgery, Nara Medical University, Kashihara, Nara 634-8522, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bone Marrow Cells / drug effects, immunology Cyclophosphamide / pharmacology* Graft vs Host Disease / drug therapy, immunology, prevention & control Heart Transplantation / immunology Immunosuppressive Agents / pharmacology* Lymphocyte Culture Test, Mixed Major Histocompatibility Complex / immunology* Rats Rats, Inbred BN Rats, Inbred Lew Survival Rate Tacrolimus / pharmacology* Transplantation Chimera / immunology* Transplantation Tolerance / drug effects* Transplantation, Homologous / immunology |
| Chemical | |
Reg. No./Substance:
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0/Immunosuppressive Agents; 109581-93-3/Tacrolimus; 50-18-0/Cyclophosphamide |
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