Mouse aorta-derived mesenchymal progenitor cells contribute to and enhance the immune response of macrophage cells under inflammatory conditions

Mouse aorta-derived mesenchymal progenitor cells contribute to and enhance the immune response of macrophage cells under inflammatory conditions

Stem Cell Research & Therapy, April 2015

25889992

Jodi F Evans, Veronica Salvador, Sheela George, Cristina Trevino-Gutierrez, Catherine Nunez

Mesenchymal progenitor cells interact with immune cells and modulate inflammatory responses. The cellular characteristics required for this modulation are under fervent investigation. Upon interaction with macrophage cells they can contribute to or suppress an inflammatory response. Current studies have focused on mesenchymal progenitors derived from bone marrow, adipose and placenta. However the arterial wall contains many mesenchymal progenitor cells and during vascular disease progression they have the potential to interact with macrophage cells. To examine the consequence of vascular-tissue progenitor cell-macrophage cell interactions in an inflammatory environment, we used a recently established mesenchymal progenitor cell line derived from the mouse aorta. Mouse bone marrow-derived macrophage cells (MΦ) and mouse aorta-derived mesenchymal progenitor cells (mAo) were cultured alone or co-cultured directly and indirectly. Cells were treated with oxidized-low density lipoprotein (ox-LDL) and/or exposed to the inflammatory mediators, lipopolysaccharide (LPS) and interferon-γ (IFNγ). A toll-like receptor-4 (TLR4) deficient macrophage cell line was used to determine the role of the mAo. To monitor inflammation, nitric oxide (NO), interleukin- 6 (IL-6) and tumor necrosis factor-α (TNFα) secretion was measured. Mesenchymal progenitor cells isolated from aorta and cloned by high proliferative capacity (mAo) can differentiate into multiple mesenchymal lineages and are positive for several commonly used mouse mesenchymal stem cell markers i.e. CD29, CD44, CD105, CD106 and Sca-1 but are negative for CD73, ecto-5'-nucleotidase. In co-culture with MΦ, they increase MΦ oxidized-LDL uptake by 52.2%. In an inflammatory environment, they synergistically and additively contribute to local production of both nitric oxide (NO) and interleukin-6 (IL-6). After exposure to ox-LDL, the inflammatory response of MΦ to LPS and LPS/IFNγ is muted. However, when lipid-laden MΦ cells are co-cultured with mAo progenitors, the muted response is recovered and the contribution by the mAo progenitor is dependent upon cell contact. The resident mesenchymal progenitor cell is a potential contributor to vascular inflammation when in contact with inflamed and lipid-laden MΦ. This interaction represents an additional target in vascular disease treatment. The potential for resident cells to contribute to the local immune response should be considered when designing therapeutics targeting inflammatory vascular disease.