G-CSF treatment of healthy pediatric donors affects their hematopoietic microenvironment through changes in bone marrow plasma cytokines and stromal cells. (March 2021)

• Record Type: Journal Article
• Authors: Aerts-Kaya, Fatima; Kilic, Emine; Köse, Sevil; Aydin, Gözde; Cagnan, Ilgin; Kuskonmaz, Baris; Uckan-Cetinkaya, Duygu
• Is Part Of: Cytokine. Volume 139(2021)
• Publication Date: 2021-03
• Subjects: Bone marrow -- Cytokines -- Hematopoietic growth factors -- Hematopoietic stem and progenitor cells -- Mesenchymal stromal cells; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2020.155407
• Languages: English
• ISSNs: 1043-4666

Abstract

Graphical abstract: Highlights: High expression of IL-16, SCGF-b, MIP-1b and RANTES pediatric BM plasma. Levels of BM plasma IL-3, IL-18, GROa, MCP-3 increased after G-CSF treatment. Levels of BM plasma RANTES decreased after G-CSF treatment. BM plasma IL2-Ra and LIF levels show negative correlation with increasing age. G-CSF treatment concomitantly increases numbers of BM hematopoietic and mesenchymal colonies. G-CSF treatment affects cumulative population doublings of MSCs. Abstract: Although G-CSF mobilized peripheral blood stem cell (PBSC) transplantation is commonly used in adults, bone marrow (BM) is still the preferred stem cell source in pediatric stem cell transplantation. Despite the fact that G-CSF is increasingly being used to enhance the hematopoietic stem/progenitor cell (HSPC) yield in BM transplantation (G-BM), the direct effects of G-CSF on the pediatric BM microenvironment have never been investigated. The BM hematopoietic niche provides the physical space where the HSPCs reside. This BM niche regulates HSPC quiescence and proliferation through direct interactions with other niche cells, including Mesenchymal Stromal Cells (MSCs). These cells have been shown to secrete a wide range of hematopoietic cytokines (CKs) and growth factors (GFs) involved in differentiation, retention and homing of hematopoietic cells. Here, we assessed changes in the BM microenvironment by measuring levels of 48 different CKs and GFs in G-BM and control BM (C-BM) plasma from pediatric donors. In addition, the effect of G-CSF on cell numbers and characteristics of HSPCs and MSCs was assessed. IL-16, SCGF-b, MIP-1b (all >1000 pg/mL) and RANTES (>10.000 pg/mL) were highly expressed in healthy donor pediatric BM plasma. Levels of IL-3, IL-18, GROa, MCP-3 (p<0.05) were increased in G-BM, whereas levels of RANTES (p<0.001) decreased after G-CSF treatment. We found a negative correlation with increasing age for IL2-Ra and LIF (p<0.05). In addition, a concomitant increase in the number of both hematopoietic and fibroblast colony forming units was observed, indicating that G-CSF affects both HSPC and MSC numbers. In conclusion, G-CSF treatment of healthy pediatric donors affects the hematopoietic BM microenvironment by expansion of HSPC and MSC numbers and modifying local CK and GF levels.