Researchers at The University of Melbourne and the company Mesoblast Ltd in Australia recently published in the journal PLOS ONE the finding that Mesoblast’s mesenchymal precursor cells (MPCs) are capable of reducing inflammation and reversing abnormal blood vessel function in an ovine model of rheumatoid arthritis (RA). The study is entitled “Effect of Mesenchymal Precursor Cells on the Systemic Inflammatory Response and Endothelial Dysfunction in an Ovine Model of Collagen-Induced Arthritis.”
RA is an autoimmune disease that leads to chronic inflammation of the joints and other parts of the body due to an overreaction of the body’s own immune system, resulting in the attack of healthy tissues. The disease is estimated to affect 1.7 million individuals in the United States and can result in painful deformity and immobility of the fingers, wrists, ankles and feet. RA patients are estimated to have a 50% higher risk of dying from cardiovascular causes than the general population. Approximately one-third of RA patients are estimated to not respond or not tolerate the current available therapies.
RA is induced by several cytokines (such as interleukin-6, interleukin-17 and TNF-alpha) that are produced by pro-inflammatory monocytes (a type of white blood cell) and activated immune T cells. It is thought that the high cardiovascular risk linked to the disease is due to persistent inflammation and endothelial cell dysfunction of the coronary arteries that leads to plaque rupture and thrombosis (obstructing blood clot).
MPCs are rare cells found around blood vessels and they are the precursors of mesenchymal stem cells. Both cell types can be expanded in culture, differentiate into different tissues, and are well tolerated when used in an allogenic way (meaning between genetically different entities but from the same species). Importantly, MPCs can induce blood vessel formation and modulate key elements of the immune system, such as pro-inflammatory monocytes and activated T cells, potentially resulting in a reduction in the levels of pro-inflammatory cytokines in the inflamed joints of RA patients.
In this study, researchers assessed the effects of an intravenous administration of MPC in 16 adult arthritic sheep regarding systemic inflammation and endothelial function. The team found that a single intravenous infusion of allogeneic MPCs in arthritic sheep was able to significantly increase the plasma levels of anti-inflammatory interleukin-10, significantly reduce plasma levels of inflammatory markers, and consequently decrease systemic inflammation. MPC treatment also reversed the abnormal endothelial dysfunction in the animal’s arteries, including the coronary arteries.
The research team concluded that MPCs represent a potential therapeutic strategy for RA as they are able to attenuate chronic inflammation, the systemic effects of the disease and potentially reduce the cardiovascular risk associated with the disorder.
“Endothelial dysfunction caused by chronic inflammation is particularly important in rheumatoid arthritis where there is a significantly increased risk of coronary artery disease and death (…). These results suggest that our intravenously delivered product candidate, MPC-300-IV, may have a clear therapeutic role in addressing the consequences of diseases of chronic systemic inflammation,” said the Mesoblast Chief Executive Silviu Itescu in a news release.
Mesoblast is currently leading a Phase 2 randomized, double-blinded, placebo-controlled, dose-escalation trial of allogeneic MPCs in 48 RA patients non-responsive to at least one biological therapy (namely interleukin-6 or TNF-alpha inhibitors) in the United States and Australia. The goal of the trial is to assess the safety, tolerability and efficacy of a single intravenous infusion of MPCs in RA patients.