Biomarker identification to assess effects of bone-marrow derived mesenchymal stromal cell-therapy in emphysema through immune profiling

Abstract

Treatment with mesenchymal stromal cells (MSC), with anti-inflammatory and regenerative capacity, may provide a therapy to halt or reverse alveolar tissue destruction in emphysema. We performed a placebo-controlled trial in emphysema patients undergoing lung volume reduction surgery before (LVRS1) and after (LVRS2) receiving bone-marrow-derived (BM-)MSC/ placebo to determine the effect on lung repair and inflammation.

Single cells were isolated from emphysematous lungs before and after MSC/placebo therapy and paired blood. We then applied mass cytometry (CyTOF) panels comprising 37/39 (myeloid/ lymphoid) antibodies to obtain a global overview of the immune cell composition. CyTOF data were analyzed in a semi-blinded manner (without information on placebo or MSC treatment, n=5/group) using Hierarchical Stochastic Neighbor Embedding (HSNE).

CyTOF analysis revealed a great number of distinct immune cell populations in human lung tissue and blood. Interestingly, compared to LVRS1, clusters of CD8 T cells (12 vs. 24% of CD45+ cells) in group A and CD4 T cells (24 vs. 40 % of CD45+ cells) in group B, increased in blood, whereas myeloid cells, NK cells, B cells and innate lymphoid cells were unaltered. Analyses on blood and lung are ongoing to further characterize alterations in immune cell composition upon MSC treatment.

We show here that CyTOF analysis of emphysematous lung tissue and blood reveals distinct features of immune populations upon MSC/ placebo treatment. We will also apply imaging mass cytometry to study cellular interactions in the lung tissue niche to better understand the underlying mechanisms of COPD.

grant: ZonMW #40-41400-98-16007