Interaction with human stromal cells enhances CXCR4 expression and engraftment of cord blood Lin-CD34- cells
Interaction with human stromal cells enhances CXCR4 expression and engraftment of cord blood Lin-CD34- cells
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DOI：
10.1016/j.exphem.2008.04.007
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发表时间：
2008-09-01
影响因子：
2.6
通讯作者：
Kato, Junji
中科院分区：
文献类型：
--
作者：
Kobune, Masayoshi;Kawano, Yutaka;Kato, Junji
Objective.造血干细胞（HSC）的移植通常通过静脉注射完成，这是一个复杂的过程，需要识别骨髓血管系统并迁移到支持性微环境。因此，一些HSC群体，包括脐带血（CB）Lin（-）CD 34（-）干细胞，不能很好地移植到非肥胖糖尿病/严重联合免疫缺陷（NOD/SCID）小鼠的骨髓（BM）中。在这项研究中，我们研究了人基质相互作用对CB Lin（-）CD 34（-）细胞特性的影响。分析新鲜CB Lin（-）CD 34（-）细胞和与人基质细胞共培养的CB Lin（-）CD 34（-）细胞上的CD 34和CXCR 4表达。使用NOD/SCID小鼠评估这些细胞的归巢活性和植入。为了鉴定间质CXCR 4诱导因子，将CB Lin（-）CD 34（-）细胞与非接触培养系统在几种底物存在下共培养。与人基质细胞共培养诱导CB Lin（-）CD 34（-）细胞表达CD 34和CXCR 4。即使在非接触培养条件下，CB Lin（-）CD 34（-）细胞上的CXCR 4表达也被诱导，表明该CXCR 4诱导因子是可溶性的。此外，CXCR 4诱导被可溶性Wnt抑制剂DKK 1抑制。经静脉注射后，这些细胞获得归巢活性并植入NOD/SCID小鼠的骨髓。这些结果可能有助于理解基质细胞在造血干细胞归巢和植入中的作用。(C)2008 ISEH -血液学和干细胞学会。由爱思唯尔公司出版
Objective. Transplantation of hematopoietic stem cells (HSCs) is usually accomplished through intravenous injection, a complex process that requires recognition of bone marrow vasculature and migration to a supportive microenvironment. Hence, some populations of HSCs, including cord blood (CB) Lin(-)CD34(-) stem cells, do not engraft well in bone marrow (BM) of nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. In this study, we examined the effect of human stromal interactions on the properties of CB Lin(-)CD34(-) cells.Materials and Methods. CD34 and CXCR4 expression on fresh CB Lin(-)CD34(-) cells and CB Lin(-)CD34(-) cells cocultured with human stromal cells were analyzed. Homing activity and engraftment of these cells were assessed using NOD/SCID mice. In an attempt to identify the stromal CXCR4-inducing factor, CB Lin(-)CD34(-) cells were cocultured with a noncontact culture system in the presence of several inhibitors.Result. Coculture with human stromal cells induced expression of CD34 and CXCR4 on CB Lin(-)CD34(-) cells. CXCR4 expression on CB Lin(-)CD34(-) cells was induced even in the noncontact culture condition, suggesting that this CXCR4-inducing factor is soluble. Moreover, CXCR4 induction was inhibited by the soluble Wnt inhibitor DKK1. Furthermore, these cells acquired homing activity and engrafted in the BM of NOD/SCID mice after intravenous injection.Conclusion. These findings maybe useful for understanding the role of stromal cells in homing and engraftment of HSCs. (C) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.