title: Interleukin-1 beta enhances human multipotent mesenchymal stromal cell proliferative potential and their ability to maintain hematopoietic precursor cells.
abstract: Multipotent mesenchymal stromal cells (MMSCs) have been demonstrated to produce mature stromal cells and maintain hematopoietic progenitor cells (HPC). It was previously demonstrated that interleukin-1 beta (IL-1 beta) stimulates the growth of the stromal microenvironment in vivo. The aim of this study was to investigate the effect of IL-1 beta treatment of human MMSCs on their proliferative potential, gene expression, immunomodulating properties, and their ability to support HPCs in vitro. Human bone marrow-derived MMSCs were cultivated in standard conditions or with IL-1 beta. The cumulative cell production was assessed for five passages. After withdrawal of IL-1 beta, MMSC clonal efficiency was investigated, and the maintenance of HPCs on top of MMSCs layers was estimated using cobblestone area forming cell (CAFC) and long-term culture initiating cell (LTC-IC) assays. The effect of untreated MMSCs or MMSCs pretreated with IL-1 beta on lymphocyte proliferation was studied by CFSE staining. The relative expression level of various genes by MMSCs was analyzed using RT-qPCR. The administration of IL-1 beta elevated MMSCs clonal efficiency and total cell production but did not affect lymphocyte proliferation. MMSCs pretreatment with IL-1 beta enhanced their ability to maintain HPCs, as detected by CAFC assay, and it altered the expression levels of genes participating in HPC regulation by stromal cells, e.g., adhesion molecules (ICAM1) and growth factors (SDF1). This study revealed the ability of IL-1 beta to stimulate MMSCs proliferation and enhance their potential to maintain HPCs. MMSCs are considered a stromal niche component in vitro. The combined in vitro and previous in vivo data suggest that IL-1 beta is a systemic regulator of the stromal microenvironment.
authors.affiliation: Laboratory Physiology of Hematopoiesis, Hematological Research Center, Ministry of Health, Noviy Zikovskiy proezd 4, Moscow 125167, Russian Federation. Electronic address: bigildeev.ae@gmail.com.
authors.forename: Alexey E
authors.initials: AE
authors.lastname: Bigildeev
authors.affiliation: Laboratory Physiology of Hematopoiesis, Hematological Research Center, Ministry of Health, Noviy Zikovskiy proezd 4, Moscow 125167, Russian Federation; MSU im. Lomonosov, Biology Department, Subdepartment Molecular Immunology, Leninskie Gory, 1, 12, Moscow 119991, Russian Federation. Electronic address: katerina.zezina@gmail.com.
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Zezina
authors.affiliation: Laboratory Physiology of Hematopoiesis, Hematological Research Center, Ministry of Health, Noviy Zikovskiy proezd 4, Moscow 125167, Russian Federation. Electronic address: iranifontova@yandex.ru.
authors.forename: Irina N
authors.initials: IN
authors.lastname: Shipounova
authors.affiliation: Laboratory Physiology of Hematopoiesis, Hematological Research Center, Ministry of Health, Noviy Zikovskiy proezd 4, Moscow 125167, Russian Federation. Electronic address: ndrize@yandex.ru.
authors.forename: Nina J
authors.initials: NJ
authors.lastname: Drize
mesh_terms: D000293:Adolescent; D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D053583:Interleukin-1beta / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; C573420:ICAM1 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016222:Fibroblast Growth Factor 2; D018799:Intercellular Adhesion Molecule-1
keywords: Gene expression; Hematopoietic precursor cells (HPC); Interleukin-1 beta; Lymphocyte proliferation; Multipotent mesenchymal stromal cells (MMSCs)