Effect of Mesenchymal Precursor Cells on the Systemic Inflammatory Response and Endothelial Dysfunction in an Ovine Model of Collagen-Induced XXXX .

@entity32 @entity625 @entity742 @entity409 @entity1812 @entity71864 @entity291
BACKGROUND AND AIM: Mesenchymal precursor cells (MPC) are reported to possess immunomodulatory properties that may prove beneficial in autoimmune and other inflammatory conditions. However, their mechanism of action is poorly understood. A collagen-induced @entity625 model has been previously developed which demonstrates @entity32 and systemic inflammatory changes. These include not only increased levels of inflammatory markers, but also vascular endothelial cell dysfunction, characterised by reduced endothelium-dependent vasodilation. This study aimed to characterise the changes in systemic inflammatory markers and endothelial function following the intravenous administration of MPC, in the ovine model. METHODS: @entity625 was induced in sixteen adult @entity742 by administration of @entity291 type II collagen into the hock joint following initial sensitisation. After 24h, @entity742 were administered either 150 million allogeneic ovine MPCs intravenously, or saline only. Fibrinogen and serum amyloid-A were measured in plasma to assess systemic @entity32 , along with pro-inflammatory and anti-inflammatory cytokines. Animals were necropsied two weeks following @entity625 induction. Coronary and digital arterial segments were mounted in a Mulvaney-Halpern wire myograph. The relaxant response to endothelium-dependent and endothelium-independent vasodilators was used to assess @entity409 . RESULTS AND CONCLUSION: Arthritic @entity742 treated with MPC demonstrated a marked spike in plasma @entity71864 , 24h following MPC administration. They also showed significantly reduced plasma levels of the inflammatory markers, fibrinogen and serum amyloid A, and increased HDL. Coronary arteries from RA @entity742 treated with MPCs demonstrated a significantly greater maximal relaxation to @entity1812 when compared to untreated RA @entity742 (253.6    17.1% of pre-contracted tone vs. 182.3    27.3% in controls), and digital arteries also demonstrated greater endothelium-dependent vasodilation. This study demonstrated that MPCs given intravenously are able to attenuate systemic inflammatory changes associated with a monoarthritis, including the development of @entity409 .
