CCL5/CCR1 axis regulates multipotency of human adipose tissue derived stromal cells

Stem Cell Res. 2013 Mar;10(2):166-78. doi: 10.1016/j.scr.2012.11.004. Epub 2012 Nov 29.

Abstract

Several potential clinical applications of stem cells rely on their capacity to migrate into sites of inflammation where they contribute to tissue regeneration processes. Inflammatory signals are partially mediated by chemokines acting via their receptors expressed on the target cells. Data concerning the repertoire and biological activities of chemokine receptors in human adipose tissue derived stromal cells (ADSCs) are limited. Here we show that CCR1 is one of the few chemokine receptors expressed in ADSCs at a high level. CCR1 expression varies in ADSCs derived from different donors. It sharply decreases in the early phase of ADSCs in vitro propagation, but further demonstrates relative stability. Expression of CCR1 positively correlates with expression of SOX2, OCT4 and NANOG, transcription factors responsible for maintenance of the stemness properties of the cells. We demonstrate that signaling via CCL5/CCR1 axis triggers migration of ADSCs, activates ERK and AKT kinases, stimulates NFκB transcriptional activity and culminates in increased proliferation of CCR1(+) cells accompanied with up-regulation of SOX2, OCT4 and NANOG expression. Our data suggest that chemokine signaling via CCR1 may be involved in regulation of stemness of ADSCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Cell Separation
  • Chemokine CCL3 / genetics
  • Chemokine CCL3 / metabolism
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / metabolism*
  • Chemokine CCL5 / pharmacology
  • Gene Expression Regulation / drug effects
  • Humans
  • Multipotent Stem Cells / cytology*
  • Multipotent Stem Cells / drug effects
  • Multipotent Stem Cells / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, CCR1 / genetics
  • Receptors, CCR1 / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Stromal Cells / cytology
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism
  • Tissue Donors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic / drug effects

Substances

  • Chemokine CCL3
  • Chemokine CCL5
  • NF-kappa B
  • RNA, Messenger
  • Receptors, CCR1
  • Transcription Factors