Failure of adult marrow-derived stem cells to generate marrow stroma after successful hematopoietic stem cell transplantation

Failure of adult marrow-derived stem cells to generate marrow stroma after successful hematopoietic stem cell transplantation
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DOI:
10.1016/s0301-472x(02)00821-4
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发表时间:
2002-08-01
影响因子:
2.6
通讯作者:
Torok-Storb, B
Torok-Storb, B
中科院分区:
医学4区
文献类型:
--
作者:
Awaya, N;Rupert, K;Torok-Storb, B

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目的。存在保留生成各种组织能力的成体骨髓源性干细胞是一个具有相当治疗潜力的诱人概念。本研究的目的是通过确定成体骨髓和外周血干细胞生成骨髓微环境基质细胞的能力来测试这种假定的可塑性程度。 患者与方法。我们检测了4名接受异基因、性别不匹配的骨髓或外周血干细胞移植后1至27年的患者的基质细胞扩增群体。培养的基质细胞通过免疫荧光和非特异性酯酶(NSE)染色以检测巨噬细胞,巨噬细胞可构成原代长期骨髓培养的重要组成部分。应用X和Y染色体的荧光原位杂交(FISH)探针区分供体细胞和宿主细胞。 结果。对重复玻片的FISH分析表明,NSE⁺细胞数量与供体来源细胞数量之间具有良好的相关性。通过对相同细胞应用NSE和FISH,并采集明场和落射荧光图像,我们证实所有供体信号均来自NSE⁺巨噬细胞。 结论。在成功的异基因干细胞移植后,即使在100%供体造血27年后,骨髓基质仍来源于宿主。(C)2002国际实验血液学学会。由爱思唯尔科学公司出版。
Objective. The existence of adult, marrow-derived stem cells that retain the ability to generate various tissues is an appealing concept that has considerable therapeutic potential. The aim of this study was to test the extent of this proposed plasticity by defining the ability of adult marrow and peripheral blood stem cells to generate stromal cells of the marrow microenvironment.Patients and Methods. We examined expanded populations of stromal cells from four patients 1 to 27 years after allogeneic, sex-mismatched marrow, or peripheral blood stem cell transplantation. The cultured stromal cells were stained by immunofluorescence and with nonspecific esterase (NSE) to detect macrophages, which can constitute a significant component of a primary long-term marrow culture. Fluorescence in situ hybridization (FISH) probes for chromosomes X and Y were applied to distinguish donor from host cells.Results. FISH analysis of replicate slides indicated a good correlation between the number of NSE+ cells and the number of donor-derived cells. By applying NSE and FISH to the same cells and capturing both bright-field and epifluorescence images, we confirmed that all donor signals were derived from NSE+ macrophages.Conclusion. After successful allogeneic stem cell transplantation, the marrow stroma remains host in origin, even after 27 years of 100% donor hematopoiesis. (C) 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc.