Dissection of the human multipotent adult progenitor cell secretome by proteomic analysis

Gregory G. Burrows, Wouter Van't Hof, Laura F. Newell, Ashok Reddy, Phillip A. Wilmarth, Larry L. David, Amy Raber, Annelies Bogaerts, Jef Pinxteren, Robert J. Deans, Richard T. Maziarz

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Multipotent adult progenitor cells (MAPCs) are adult adherent stromal stem cells currently being assessed in acute graft versus host disease clinical trials with demonstrated immunomodulatory capabilities and the potential to ameliorate detrimental autoimmune and inflammation-related processes. Our previous studies documented that MAPCs secrete factors that play a role in regulating T-cell activity. Here we expand our studies using a proteomics approach to characterize and quantify MAPC secretome components secreted over 72 hours in vitro under steady-state conditions and in the presence of the inflammatory triggers interferon-γ and lipopolysaccharide, or a tolerogenic CD74 ligand, RTL1000. MAPCs differentially responded to each of the tested stimuli, secreting molecules that regulate the biological activity of the extracellular matrix (ECM), including proteins that make up the ECM itself, proteins that regulate its construction/deconstruction, and proteins that serve to attach and detach growth factors from ECM components for redistribution upon appropriate stimulation. MAPCs secreted a wide array of proteases, some detectable in their zymogen forms. MAPCs also secreted protease inhibitors that would regulate protease activity. MAPCs secreted chemokines and cytokines that could provide molecular guidance cues to various cell types, including neutrophils, macrophages, and T cells. In addition, MAPCs secreted factors involved in maintenance of a homeostatic environment, regulating such diverse programs as innate immunity, angiogenesis/angiostasis, targeted delivery of growth factors, and the matrix-metalloprotease cascade.

Original languageEnglish (US)
Pages (from-to)745-757
Number of pages13
JournalStem Cells Translational Medicine
Volume2
Issue number10
DOIs
StatePublished - Oct 2013

Keywords

  • Adult hematopoietic stem cells
  • Graft versus host disease
  • Immunotherapy
  • Mesenchymal stem cells
  • Proteomics
  • RTL1000
  • Tolerance

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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