Mesenchimal stromal cells as rescue therapy for refractory Chronic Lung Allograft Dysfunction: preliminary data of an Italian monocentric cohort

Background: Allogenic bone marrow derived mesenchimal stromal cells (Allo-BM MSCs) represent a promising therapy for chronic lung allograft dysfunction (CLAD) after lung transplantation, due to their immunomodulatory and tolerogenic properties, as shown in preclinical and clinical models and small monocentric case series(Chambers DC et al, doi: 10.1002/sctm.16-0372). Methods: Five patients with advanced CLAD and progressive functional deterioration, which experienced all possible treatment lines, underwent monthly infusion of allo-BM MSCs ( 106cells per kilogram) as salvage treatment. Beside recording clinical follow up and lung function, we analysed serum levels of miR-21 and IL-4,IL2,IP-10,IL-1beta, TNF-alpha, MCP-1,IL-17 A, IL-6,IL-10,IFN-gamma, il-12p70 and IL8 at 0-6 months treatment. Results:: After initiation of therapy with MSCs, FEV1 stabilized in 4 patients and slowered decline in 1 patient (graph 1). No adverse effects attributable to MSCs therapy, no increase in the frequency of infections and no significant change in cytokines and miR levels were detected. Conclusion: Monthly intravenous treatment with low dose of Allo-BM MSCs is well tolerated, and functional results on a small cohort of patients suggest that might stabilize graft function even in lung recipients with advanced CLAD.