Kinetics of central nervous system microglial and macrophage engraftment: Analysis using a transgenic bone marrow transplantation model
Kinetics of central nervous system microglial and macrophage engraftment: Analysis using a transgenic bone marrow transplantation model
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DOI：
10.1182/blood.v90.3.986.986_986_993
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发表时间：
1997-08-01
期刊：
影响因子：
20.3
通讯作者：
Abkowitz, JL
中科院分区：
文献类型：
--
作者：
Kennedy, DW;Abkowitz, JL
为了确定骨髓移植后组织巨噬细胞和小胶质细胞植入的动力学，我们利用ROSA 26小鼠建立了一个模型。移植的ROSA 26细胞可以在受体动物中精确鉴定，因为它们组成性地表达β -半乳糖苷酶（β -gal）和新霉素抗性。b6 / 129f2小鼠照射后，移植ROSA 26供体的骨髓及其组织（脾、骨髓、脑、肝和肺），在不同时间点检查，以确定植入动力学。对移植动物的冷冻切片进行组织化学染色以鉴定供体细胞。在移植后1、2、6和12个月，通过β -gal染色和新霉素耐药性检测，98%至100%的粒细胞-巨噬细胞菌落为供体（ROSA 26）来源。1个月时脾脏单核/巨噬细胞89%来自供体，证实了造血组织的快速和完全植入。此时只观察到罕见的ROSA 26组织巨噬细胞或小胶质细胞。肺泡巨噬细胞在移植后2个月明显植入，并在移植后1年增加到总组织巨噬细胞的61%。肝库普弗细胞移植的动力学与肺中的相似。然而，供体小胶质细胞移植在6个月时仅占总小胶质细胞的23%，1年后仅增加到30%。此外，供体小胶质细胞主要见于血管周围和小脑膜，而非实质部位。数据显示，小胶质细胞来源于BM前体，但翻转速度明显慢于其他组织巨噬细胞。在ROSA 26bm受体中未观察到临床或组织学上的移植物抗宿主病。这些动力学可能影响溶酶体贮积病的基因治疗策略。由于单个供体细胞可以在现场识别，ROSA 26模型应该在移植生物学中有许多应用，包括归巢和分化的研究。(C) 1997年由美国血液病学会出版。
To determine the kinetics of tissue macrophage and microglial engraftment after bone marrow (BM) transplantation, we have developed a model using the ROSA 26 mouse. Transplanted ROSA 26 cells can be precisely identified in recipient animals because they constitutively express beta-galactosidase (beta-gal) and neomycin resistance. B6/129 F2 mice were irradiated and transplanted with BM from ROSA 26 donors and their tissues (spleen, marrow, brain, liver, and lung) examined at various time points to determine the kinetics of engraftment. Frozen sections from transplanted animals were stained histochemically for beta-gal to identify donor cells. At 1, 2, 6, and 12 months posttransplantation, 98% to 100% of granulocyte-macrophage colonies were of donor (ROSA 26) origin determined by beta-gal staining and by neomycin resistance. Splenic monocytes/macrophages were 89% donor origin by 1 month confirming quick and complete engraftment of hematopoietic tissues. At this time, only rare ROSA 26 tissue macrophages or microglia were observed. Alveolar macrophage engraftment was evident by 2 months and had increased to 61% of total tissue macrophages at 1 year posttransplantation. The kinetics of liver Kupffer cell engraftment were similar to those seen in the lung. However, donor microglial engraftment remained only 23% of total microglia at 6 months and increased to only 30% by 1 year. Also, donor microglia were predominantly seen at perivascular and leptomeningeal, and not parenchymal, sites. The data show that microglia derive from BM precursors but turn over at a significantly slower rate than other tissue macrophages. No clinical or histological graft-versus-host disease was observed in the recipients of ROSA 26 BM. These kinetics may impact strategies for the gene therapy of lysosomal storage diseases. Because individual donor cells can be identified in site, the ROSA 26 model should have many applications in transplantation biology including studies of homing and differentiation. (C) 1997 by The American Society of Hematology.