Interaction with human stromal cells enhances CXCR4 expression and engraftment of cord blood Lin⁻CD34⁻ cells

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.