title: 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.
authors.affiliation: Stem Cells Laboratory, Bambino Gesù Children's Hospital, Scientific Institute (IRCCS), Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Rofani
authors.forename: Luisella
authors.initials: L
authors.lastname: Luchetti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Testa
authors.forename: Rosa
authors.initials: R
authors.lastname: Lasorella
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Isacchi
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Bottazzo
authors.forename: Anna C
authors.initials: AC
authors.lastname: Berardi
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019410:Interleukin-16 / Q000494:pharmacology*; D051379:Mice; D019718:Receptors, CXCR4 / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; C527276:CXCR4 protein, human; D019410:Interleukin-16; D019718:Receptors, CXCR4