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Stem Cells. 2018 Nov 28. doi: 10.1002/stem.2955. [Epub ahead of print]

TAFA2 induces skeletal (stromal) stem cell migration through activation of Rac1-p38 signaling.

Author information

1
Department of Cellular and Molecular Medicine, Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen, Copenhagen, Denmark.
2
Molecular Endocrinology & Stem Cell Research Unit (KMEB), Department of Endocrinology and Metabolism, Odense University Hospital & University of Southern Denmark, Odense, Denmark.
3
Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Saudi Arabia.
4
Department of Haematology, Aalborg University, Aalborg, Denmark.
5
Biological Sciences Department, College of Science, King Faisal University, Hofuf, Saudi Arabia.
6
Bioneer A/S, Hørsholm, Denmark.

Abstract

Understanding the mechanisms regulating recruitment of human skeletal (stromal or mesenchymal) stem cells (hMSC) to sites of tissue injury is a prerequisite for their successful use in cell replacement therapy. Chemokine-like protein TAFA2 is a recently discovered neurokine involved in neuronal cell migration and neurite outgrowth. Here, we demonstrate a possible role for TAFA2 in regulating recruitment of hMSC to bone fracture sites. TAFA2 increased the in vitro trans-well migration and motility of hMSC in a dose-dependent fashion and induced significant morphological changes including formation of lamellipodia as revealed by high content image analysis at single cell level. Mechanistic studies revealed that TAFA2 enhanced hMSC migration through activation of the Rac1-p38 pathway. In addition, TAFA2 enhanced hMSC proliferation, whereas differentiation of hMSC toward osteoblast and adipocyte lineages was not altered. In vivo studies demonstrated transient upregulation of TAFA2 gene expression during the inflammatory phase of fracture healing in a closed femoral fracture model in mice and a similar pattern was observed in serum levels of TAFA2 in patients following hip fracture. Finally, IL-1β was found as an upstream regulator of TAFA2 expression. Our findings demonstrate that TAFA2 enhances hMSC migration and recruitment and thus is relevant for regenerative medicine applications.

KEYWORDS:

Fracture healing; Mesenchymal Stem (Stromal) Cell; Migration; Regenerative medicine; TAFA2

PMID:
30485583
DOI:
10.1002/stem.2955

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