Growth factors mobilize CXCR4 low/negative primitive hematopoietic stem/progenitor cells from the bone marrow of nonhuman primates
Growth factors mobilize CXCR4 low/negative primitive hematopoietic stem/progenitor cells from the bone marrow of nonhuman primates
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DOI：
10.1016/j.bbmt.2004.07.002
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发表时间：
2004-10-01
影响因子：
4.3
通讯作者：
Hoffman, R
中科院分区：
文献类型：
--
作者：
Mahmud, N;Patel, H;Hoffman, R
趋化因子受体CXCR4由CD34(+)造血干/祖细胞(HSC/HPC)表达。一些研究人员认为 CXCR4 的表达可能是 HSC/HPC 的一个重要特征。我们在临床相关的非人灵长类动物模型狒狒（狒狒）中研究了生长因子诱导的 HSC 动员过程中 CXCR4 的动态表达。我们评估了 HSC/HPC 中 CXCR4 的表达在稳态造血过程以及生长因子诱导的动员过程中是否发生变化。用生长因子动员 5 只狒狒的外周血干细胞。在动员过程中，外周血CD34(+)细胞CXCR4(-)的比例持续逐步增加。外周血中CD34(+)CXCR4(-)细胞的最高数量与可测定的集落形成细胞的最大数量同时出现。 CD34(+)CXCR4(-)细胞群的克隆效率是CD34(+)CXCR4(+)细胞的3倍，CD34(+)CXCR4(-)细胞群中鹅卵石区域形成细胞的频率是CD34(+)CXCR4(+)细胞的6倍。此外，基于低 Hoechst 3 3342 (Ho) 和罗丹明 123 (Rho) 染色 (Ho-Low/Rho(Low)) 分离的最静止的 CD34(+) 细胞在 CXCR4(Low/-) 细胞群中高度富集。动员的外周血CD34(+)细胞与生长因子离体孵育40小时导致表达CXCR4的细胞数量增加。含有主要由CXCR4-细胞组成的CD34(+)细胞的外周血干细胞移植物能够快速植入受到致命辐射的狒狒。由于动员的外周血移植物中绝大多数 CD34(+) 细胞是 CXCR4-，并且能够拯救受到致命辐射的狒狒，因此 CXCR4 的体外表达似乎不太可能是 HSC 归巢和植入的绝对要求。总之，我们的数据表明，在生长因子诱导的 HSC/HPC 动员过程中，CD34(+) 细胞上 CXCR4 表达的动态性质。此外，我们的数据表明CXCR4表达的缺乏可能是相对更原始的HSC/HPC的一个特征，其特征是较高的增殖能力。 (C) 2004 年美国血液和骨髓移植协会。
The chemokine receptor CXCR4 is expressed by CD34(+) hematopoietic stem/progenitor cells (HSC/HPC). Several investigators have suggested that expression of CXCR4 may be an important characteristic of HSC/HPC. We studied the dynamic expression of CXCR4 during growth factor-induced mobilization of HSC in a clinically relevant nonhuman primate model, Papio anubis (baboons). We evaluated whether CXCR4 expression in HSC/HPC varies during steady-state hematopoiesis as well as during growth factor-induced mobilization. Peripheral blood stem cells from 5 baboons were mobilized with growth factors. During mobilization, there was a consistent stepwise increase in the proportion of peripheral blood CD34(+) cells that were CXCR4(-). The highest number of CD34(+)CXCR4(-) cells appeared in the peripheral blood at the same time as the maximum number of assayable colony-forming cells. The cloning efficiency of the CD34(+)CXCR4(-) population was 3-fold greater than that of CD34(+)CXCR4(+) cells, and the frequency of cobblestone area-forming cells was 6 times higher in the CD34(+)CXCR4(-) population in comparison to CD34(+)CXCR4(+) cells. Furthermore, the most quiescent CD34(+) cells isolated on the basis of low Hoechst 3 3342 (Ho) and rhodamine 123 (Rho) staining (Ho-Low/Rho(Low)) were highly enriched in the CXCR4(Low/-) cell population. Ex vivo incubation of mobilized peripheral blood CD34(+) cells with growth factors for 40 hours resulted in increasing numbers of cells expressing CXCR4. Peripheral blood stem cell grafts containing CD34(+) cells that consisted of predominantly CXCR4- cells were able to rapidly engraft lethally irradiated baboons. Because the overwhelming number of CD34(+) cells within the mobilized peripheral blood grafts were CXCR4- and were capable of rescuing lethally irradiated baboons, it seems unlikely that the expression of CXCR4 in vitro is an absolute requirement for HSC homing and engraftment. In summary, our data suggest the dynamic nature of CXCR4 expression on CD34(+) cells during growth factor-induced HSC/HPC mobilization. In addition, our data indicate that the lack of CXCR4 expression is possibly a characteristic of relatively more primitive HSC/HPC characterized by a higher proliferative capacity. (C) 2004 American Society for Blood and Marrow Transplantation.