Donor hematopoietic progenitor cells in nonmyeloablated rat recipients of allogeneic bone marrow and liver grafts.
Donor hematopoietic progenitor cells in nonmyeloablated rat recipients of allogeneic bone marrow and liver grafts.
复制标题
同种异体骨髓和肝移植的非清髓大鼠受体中的供体造血祖细胞。
DOI：
10.1097/00007890-199903270-00009
复制
发表时间：
1999
期刊：
影响因子：
6.2
通讯作者：
Murase,N
中科院分区：
文献类型：
--
作者：
Sakamoto,T;Ye,Q;Lu,L;Demetris,AJ;Starzl,TE;Murase,N
背景：尽管在长期存活的器官移植受者中，多谱系微嵌合体的持续存在意味着迁移性多能供体干细胞的植入，方法：在未接受过刘易斯（LEW）的大鼠和Brown Norway（BN）受体的骨髓和非实质肝细胞中证实了祖细胞。通过半定量培养集落形成单位（CFU-C）测定同种异体移植物。骨髓细胞（BMC）（2.5× 108）、原位肝脏或异位心脏（腹部部位）的LEW同种异体移植物在每日他克莫司治疗2周的情况下移植，并在第20天和第27天额外单次给药。供体CFU-C集落与受体集落在同种异体移植物和受体骨髓中用供体特异性MHC II类单克隆抗体区分。供体和受体集落的比例估计从一个标准曲线创建的LEW和BN骨髓混合物的已知concentration.Results.After的BMC输注，5-10%的CFU-C在骨髓的BN收件人是LEW表型在移植后14，30和60天。然而，在100天时，在该部位不再发现供体CFU-C。BN肝移植受者骨髓中LEW CFU-C的分布与2.5× 108 BMC移植受者相似，但供体集落仅为移植受者的1/20 ~ 1/200。这是预期的，因为单个肝脏的乘客白细胞中的祖细胞与1-5× 10 6 BMC中的祖细胞相当。使用液体CFU-C测定，供体祖细胞被证明在肝移植物的非实质细胞长达100天。相反，在心脏移植后，供体CFU-C不能在受体骨髓中被识别，即使在14d.Conclusion.在有效的免疫抑制下，异基因造血祖细胞有效地与宿主细胞竞争在非细胞清除受体的骨髓中的初始植入，但在移植后60至100天之间从该位置消失，这与我们先前在该模型中观察到的供体白细胞嵌合体从淋巴样区室向非淋巴样区室的转移相一致。同种异体肝移植物的同系实质环境可能是供肝祖细胞持续存在的特殊场所。
Background.Although the persistence of multilineage microchimerism in recipients of long-surviving organ transplants implies engraftment of migratory pluripotent donor stem cells, the ultimate localization in the recipient of these cells has not been determined in any species.Methods.Progenitor cells were demonstrated in the bone marrow and nonparenchymal liver cells of naive rats and in Brown Norway (BN) recipients of Lewis (LEW) allografts by semiquantitative colony-forming unit in culture (CFU-C) assays. The LEW allografts of bone marrow cells (BMC)(2.5× 10 8), orthotopic livers, or heterotopic hearts (abdominal site) were transplanted under a 2-week course of daily tacrolimus, with additional single doses on days 20 and 27. Donor CFU-C colonies were distinguished from recipient colonies in the allografts and recipient bone marrow with a donor-specific MHC class II monoclonal antibody. The proportions of donor and recipient colonies were estimated from a standard curve created by LEW and BN bone marrow mixtures of known concentrations.Results.After the BMC infusions, 5-10% of the CFU-C in the bone marrow of BN recipients were of the LEW phenotype at 14, 30, and 60 days after transplantation. At 100 days, however, donor CFU-C could no longer be found at this site. The pattern of LEW CFU-C in the bone marrow of BN liver recipients up to 60 days was similar to that in recipients of 2.5× 10 8 BMC, although the donor colonies were only 1/20 to 1/200 as numerous. This was expected, because the progenitor cells in the passenger leukocytes of a single liver are equivalent to those in 1-5× 10 6 BMC. Using a liquid CFU-C assay, donor progenitor cells were demonstrated among the nonparenchymal cells of liver allografts up to 100 days. In contrast, after heart transplantation, donor CFU-C could not be identified in the recipient bone marrow, even at 14 days.Conclusion.Under effective immunosuppression, allogeneic hematopoietic progenitors compete effectively with host cells for initial engraftment in the bone marrow of noncytoablated recipients, but disappear from this location between 60 and 100 days after transplantation, coincident with the shift of donor leukocyte chimerism from the lymphoid to the nonlymphoid compartment that we previously have observed in this model. It is possible that the syngeneic parenchymal environment of the liver allografts constitutes a privileged site for persistent progenitor donor cells.