Open AccessTAFA2 Induces Skeletal (Stromal) Stem Cell Migration Through Activation of Rac1‐p38 Signaling
Author(s) -
Jafari Abbas,
Isa Adiba,
Chen Li,
Ditzel Nicholas,
Zaher Walid,
Harkness Linda,
Johnsen Hans E.,
Abdallah Basem M.,
Clausen Christian,
Kassem Moustapha
Publication year - 2019
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2955
Subject(s) - microbiology and biotechnology , biology , mesenchymal stem cell , rac1 , stem cell , stromal cell , osteoblast , regenerative medicine , cell migration , neurite , cellular differentiation , cell , signal transduction , cancer research , in vitro , biochemistry , genetics , gene
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 after hip fracture. Finally, interleukin‐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. S tem C ells 2019;37:407–416