title: Dissection of the human multipotent adult progenitor cell secretome by proteomic analysis.
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.
authors: Department of Neurology.
authors: Gregory G
authors: GG
authors: Burrows
authors: Wouter
authors: W
authors: Van't Hof
authors: Laura F
authors: LF
authors: Newell
authors: Ashok
authors: A
authors: Reddy
authors: Phillip A
authors: PA
authors: Wilmarth
authors: Larry L
authors: LL
authors: David
authors: Amy
authors: A
authors: Raber
authors: Annelies
authors: A
authors: Bogaerts
authors: Jef
authors: J
authors: Pinxteren
authors: Robert J
authors: RJ
authors: Deans
authors: Richard T
authors: RT
authors: Maziarz
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D039902:Multipotent Stem Cells / Q000378:metabolism*; D020543:Proteome
chemical_list: D020543:Proteome
keywords: Adult hematopoietic stem cells; Graft versus host disease; Immunotherapy; Mesenchymal stem cells; Proteomics; RTL1000; Tolerance
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