IL-16 Can Synergize With Early Acting Cytokines to Expand Ex Vivo CD34 + Isolated from Cord Blood

Abstract

We previously reported that interleukin (IL)-16 can induce CD34⁺ hematopoietic cells to proliferate and differentiate in vitro into phenotypically and functionally mature dendritic cells. In this study, we investigated the effects of IL-16 on the expansion of CD34⁺ cells from human cord blood (CB). CD34⁺ CB cells were cultured for 14 days in medium containing a basal cocktail (BC) containing stem cell factor, Flt-3 ligand, thrombopoietin, IL-6, and IL-3 with and without IL-16 as a control. Interleukin-16 added to BC significantly enhanced the expansion of CD34⁺ cells (66.47 ± 1.46-fold vs. 36.23 ± 1.67-fold), as well as CD34⁺CD38⁻ early stem cells (106.67 ± 2.34-fold vs. 63.42 ± 1.89-fold) and progenitor cells [colony-forming unit (CFU) -mixed -(GEMM)] and multilineage-committed progenitors [burst-forming unit (BFU-E), CFU–granulocyte, macrophage (-GM), CFU-megakaryocyte (-MK)]. Interleukin-16 also significantly increased long-term culture–initiating cells (160.8 ± 3.45-fold vs. 83 ± 2.89-fold with BC alone). Moreover, CD34⁺ cells expanded with IL-16 maintained the capacity to differentiate into the lymphoid-B and -NK lineage. The addition of IL-16 to BC increased the migratory capacity of expanded CD34⁺ cells compared to BC alone, leaving the expression of CXCR4 unaffected, and decreased the percentage of CD34⁺CD4⁺ cells. We showed that IL-16 released endogenously affected the ex vivo expansion of CD34⁺ cells. Overall, this study suggests that IL-16 may have a new role in promoting the expansion of hematopoietic stem cells and may represent a new tool for the expansion of CD34⁺ cells for clinical applications.