IFN-g and TNF-a Pre-licensing Protects Mesenchymal Stromal Cells from the
Pro-inflammatory Effects of Palmitate.
Authors Boland L, Burand AJ, Brown AJ, Boyt D, Lira VA, Ankrum JA
Submitted By James Ankrum on 2/19/2018
Status Published
Journal Molecular therapy : the journal of the American Society of Gene Therapy
Year 2017
Date Published
Volume : Pages Not Specified : Not Specified
PubMed Reference 29352647
Abstract The use of mesenchymal stromal cell (MSC) therapy for the treatment of type 2
diabetes (T2D) and T2D complications is promising; however, the investigation of
MSC function in the setting of T2D has not been thoroughly explored. In our
current study, we investigated the phenotype and function of MSCs in a simulated
in vitro T2D environment. We show that palmitate, but not glucose, exposure
impairs MSC metabolic activity with moderate increases in apoptosis, while
drastically affecting proliferation and morphology. In co-culture with
peripheral blood mononuclear cells (PBMCs), we found that MSCs not only lose
their normal suppressive ability in high levels of palmitate, but actively
support and enhance inflammation, resulting in elevated PBMC proliferation and
pro-inflammatory cytokine release. The pro-inflammatory effect of MSCs in
palmitate was partially reversed via palmitate removal and fully reversed
through pre-licensing MSCs with interferon-gamma and tumor necrosis factor
alpha. Thus, palmitate, a specific metabolic factor enriched within the T2D
environment, is a potent modulator of MSC immunosuppressive function, which may
in part explain the depressed potency observed in MSCs isolated from T2D
patients. Importantly, we have also identified a robust and durable
pre-licensing regimen that protects MSC immunosuppressive function in the
setting of T2D.

Investigators with authorship
James AnkrumUniversity of Iowa