Circulating healing (CH) cells expressing BST2 are functionally activated by the injury-regulated systemic factor HGFA

Stem Cell Res Ther. 2018 Nov 8;9(1):300. doi: 10.1186/s13287-018-1056-1.

Abstract

Background: Restoration of damaged tissues through the activation of endogenous progenitors is an attractive therapeutic option. A deep evaluation of the intrinsic stem/progenitor cell properties as well as the reciprocal interactions with injured environments is of critical importance.

Methods: Here, we show that bone marrow stromal cell antigen 2 (BST2) allows the isolation of a population of circulating progenitors, the circulating healing (CH) cells, characterized by a distinctive core signature. The bone marrow (BM) origin of BST2pos CH cells has been strengthened by the co-expression of leptin receptor, the hallmark of a subpopulation of BM-skeletal stem cells.

Results: BST2pos CH cells retained the capacity to (i) respond to injury signals generated by a bone fracture, (ii) modify the expression of cell motility genes following damage, and (iii) react to hepatocyte growth factor-activator (HGFA), an injury-related stimulus sufficient to induce their transition into GALERT, a state in which cells are functionally activated and participate in tissue repair.

Conclusions: Taken together, these results could pave the way for the identification of new strategies to enhance and potentiate endogenous regenerative mechanisms for future therapies.

Keywords: Endogenous regeneration; Hepatocyte growth factor-A; Injury-regulated stimuli; Progenitor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism*
  • Biomarkers / metabolism
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / drug effects
  • Cell Size / drug effects
  • Gene Expression Profiling
  • Membrane Glycoproteins / metabolism*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Organ Specificity
  • Serine Endopeptidases / pharmacology*
  • Wound Healing* / drug effects
  • Wounds and Injuries / pathology*

Substances

  • Antigens, CD
  • BST2 protein, mouse
  • Biomarkers
  • Membrane Glycoproteins
  • HGF activator
  • Serine Endopeptidases