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  • Title: Interaction with human stromal cells enhances CXCR4 expression and engraftment of cord blood Lin(-)CD34(-) cells.
    Author: Kobune M, Kawano Y, Takahashi S, Takada K, Murase K, Iyama S, Sato T, Takimoto R, Niitsu Y, Kato J.
    Journal: Exp Hematol; 2008 Sep; 36(9):1121-31. PubMed ID: 18562079.
    Abstract:
    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 may be useful for understanding the role of stromal cells in homing and engraftment of HSCs.
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