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The role of cyclophosphamide and granulocyte colony‐stimulation factor in achieving high‐level chimerism in allotransplanted limbs
Author(s) -
Muramatsu Keiichi,
YouXin Song,
Hashimoto Takahiro,
Matsunaga Tsunemitsu,
Taguchi Toshihiko
Publication year - 2006
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.20240
Subject(s) - cyclophosphamide , allotransplantation , granulocyte colony stimulating factor , granulocyte , medicine , transplantation , stimulation , bone marrow , immunology , chemotherapy
The establishment of a high‐level of chimerism may be the most stable strategy for donor‐specific tolerance. The purpose of this study was to evaluate the efficacy of a new protocol using cyclophosphamide (CYP) and granulocyte colony‐stimulation factor (G‐CSF) to induce high‐level chimerism following rat whole‐limb allotransplantation. Seventy‐three whole‐limb allotransplants from LacZ transgenic rats to LEW rats were performed. CYP was injected at day 2, and G‐CSF was given from day 0 to 3. Nontreated limb allografts were rejected after 4.2 days. In FK506‐treated group for 28 days, the survival time was prolonged to 64 days. In the group treated with CYP/G‐CSF, limb allografts were rejected after 5.4 days and 5 of 15 recipients showed acute lethal graft‐versus‐host disease (GVHD). Polymerase chain reaction (PCR) study showed a high level of chimerism even within 1 week after transplantation. Fourteen of 30 recipients given CYP/G‐CSF/FK506 died within 2 weeks. The limb survival was significantly prolonged, however, with three grafts surviving more than 300 days. Seven recipients (24%) showed chronic GVHD. A high‐level of chimerism was maintained when limb allografts were not rejected by recipients. Limb allografting could function as a vascularized carrier for bone marrow transplantation, provide a continuous source of donor cells and contribute to a high level of chimerism in the recipient. Pretransplant CYP followed by G‐CSF and FK506 treatment significantly prolonged the survival of limb allografts but frequently caused chronic GVHD in the recipients. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:2133–2140, 2006