Interactome Analysis of iPSC Secretome and Its Effect on Macrophages In Vitro

Int J Mol Sci. 2021 Jan 19;22(2):958. doi: 10.3390/ijms22020958.


Induced pluripotent stem cell secretome (iPSC-CM) mitigate organ injury and help in repair. Macrophages play a critical role in tissue repair and regeneration and can be directed to promote tissue repair by iPSC-CM, although the exact mechanisms are not known. In the current investigative study, we evaluated the possible mechanism by which iPSC-CM regulates the phenotype and secretory pattern of macrophages in vitro. Macrophages were obtained from human peripheral blood mononuclear cells and differentiated to various subpopulations and treated with either iPSC-CM or control media in vitro. Macrophage phenotype was assessed by flow cytometry, gene expression changes by qRT PCR and secretory pattern by multiplex protein analysis. The protein and gene interaction network revealed the involvement of Amyloid precursor protein (APP) and ELAV-like protein 1 (ELAVL-1) both present in the iPSC-CM to play an important role in regulating the macrophage phenotype and their secretory pattern. This exploratory study reveals, in part, the possible mechanism and identifies two potential targets by which iPSC-CM regulate macrophages and help in repair and regeneration.

Keywords: induced pluripotent stem cells; lung fibrosis; lung repair and regeneration; macrophages; stem cells secretome.

MeSH terms

  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Culture Media, Conditioned / analysis
  • Culture Media, Conditioned / chemistry
  • Culture Media, Conditioned / metabolism
  • Culture Media, Conditioned / pharmacology
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism*
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / physiology
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / physiology
  • Protein Interaction Maps
  • Proteome* / analysis
  • Proteome* / metabolism
  • Proteome* / pharmacology


  • Culture Media, Conditioned
  • Proteome