"Prevalence of liver disease is c6% (29 million people) in the EU with mortality rates from chronic liver diseases estimated at 14.3 per 100.000 in the EU-25 in 2004. Most liver diseases have a significant inflammatory component that underpins liver damage and fibrogenesis, yet current therapies have limited effectiveness. Safe novel anti-inflammatory therapies would satisfy a large unmet need for inflammatory liver conditions such as primary sclerosing cholangitis (PSC). Mesenchymal Stromal Cells (MSC) are a mixed population of plastic-adherent (PA) cells isolated from bone marrow, umbilical cord and adipose tissue. Preclinical studies show that intravenous administration of PA-MSC reduces liver inflammation/damage, however only one MSC-based clinical study has been reported to date.MERLIN will examine if MSC can safely reduce biliary damage in mouse models followed by a clinical study in patients with PSC. We have identified an antibody (S2) that isolates comparable MSC from human & mouse marrow, enabling testing of pure functionally distinct cell S2+ & S2- and PA-MSC populations. We will use the world’s first GMP-compliant non-bead-based cell sorter to select S2+ MSC to comply with future therapeutic regulatory requirements. MERLIN partners will use novel methods to enhance MSC efficacy in PSC - by reducing immune clearance of MSC & by promoting MSC functionality & localisation in vivo.We will assess if MSC sub-sets exert differing levels of control upon liver inflammation in pre-clinical models, as well as defining their proliferation and mechanism of action. We will develop entirely novel biomarkers for PSC within the disease pathway pre and post cell infusion. The optimal combination of MSC sub-set and “efficacy enhancement”, will be selected for progression to a Phase 2 clinical safety study in patients with PSC.MERLIN will deliver a comprehensive data-set on optimised purified MSC and their efficacy/safety in pre-clinical models prior to a clinical trial in patients with PSC."