Platelet-Derived Stromal Cell-Derived Factor-1 Is Required for the Transformation of Circulating Monocytes into Multipotential Cells

Noriyuki Seta,Hiroshi Miyazaki,Masataka Kuwana,Yuka Okazaki,Takashi Kato,Carol Feghali-Bostwick

doi:10.1371/journal.pone.0074246

Noriyuki Seta, Hiroshi Miyazaki + Show 4 more

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https://doi.org/10.1371/journal.pone.0074246

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Journal: PloS one	Publication Date: Sep 16, 2013
Citations: 35	License type: CC BY 4.0

Affiliation: Keio University, Kyowa Kirin (Japan), Waseda University

Abstract

BackgroundWe previously described a primitive cell population derived from human circulating CD14+ monocytes, named monocyte-derived multipotential cells (MOMCs), which are capable of differentiating into mesenchymal and endothelial lineages. To generate MOMCs in vitro, monocytes are required to bind to fibronectin and be exposed to soluble factor(s) derived from circulating CD14− cells. The present study was conducted to identify factors that induce MOMC differentiation.MethodsWe cultured CD14+ monocytes on fibronectin in the presence or absence of platelets, CD14− peripheral blood mononuclear cells, platelet-conditioned medium, or candidate MOMC differentiation factors. The transformation of monocytes into MOMCs was assessed by the presence of spindle-shaped adherent cells, CD34 expression, and the potential to differentiate in vitro into mesenchymal and endothelial lineages.ResultsThe presence of platelets or platelet-conditioned medium was required to generate MOMCs from monocytes. A screening of candidate platelet-derived soluble factors identified stromal cell-derived factor (SDF)-1 as a requirement for generating MOMCs. Blocking an interaction between SDF-1 and its receptor CXCR4 inhibited MOMC generation, further confirming SDF-1′s critical role in this process. Finally, circulating MOMC precursors were found to reside in the CD14+CXCR4high cell population.ConclusionThe interaction of SDF-1 with CXCR4 is essential for the transformation of circulating monocytes into MOMCs.

Highlights

Circulating CD14+ monocytes, which are heterogeneous in terms of surface markers, phagocytic capacity, and differentiation potential, are committed precursors in transit from the bone marrow to their ultimate site of activity [1]
Our previous research indicated that to generate monocyte-derived multipotential cells (MOMCs) from circulating CD14+ monocytes in vivo, the monocytes are required to bind to fibronectin’s RGD domain via a5b1 integrin on the monocytes’ cell surface, and are required to be exposed to soluble factor(s) derived from the circulating CD142 cell fraction [9,15]
We previously reported that to generate MOMCs, circulating CD14+ monocytes are required to bind to fibronectin and be exposed to peripheral blood CD142 cells [9]

Summary

Introduction

Circulating CD14+ monocytes, which are heterogeneous in terms of surface markers, phagocytic capacity, and differentiation potential, are committed precursors in transit from the bone marrow to their ultimate site of activity [1]. We previously identified a peripheral bloodderived cell population, termed monocyte-derived multipotential cells (MOMCs), that have a fibroblast-like morphology in culture and a unique phenotype positive for CD14, CD45, CD34, and type I collagen [9]. This population originates from circulating CD14+ monocytes, and contains primitive cells that can differentiate into cells with the typical phenotypes and functions of mesenchymal cells, neurons, and endothelium in vitro [8,9,10,11,12]. The present study was conducted to identify factors that induce MOMC differentiation

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