CD317-Positive Immune Stromal Cells in Human “Mesenchymal Stem Cell” Populations
Alasdair G. Kay, James M. Fox, James P. Hewitson, Andrew P. Stone, Sophie Robertson, Sally James, Xiaonong Wang, Elizabeth Kapasa, Xuebin Yang, Paul Genever
Abstract
Heterogeneity of bone marrow mesenchymal stromal cells (MSCs, frequently referred to as “mesenchymal stem cells”) clouds biological understanding and hampers their clinical development. In MSC cultures most commonly used in research and therapy, we have identified an MSC subtype characterized by CD317 expression (CD317 pos (29.77 ± 3.00% of the total MSC population), comprising CD317 dim (28.10 ± 4.60%) and CD317 bright (1.67 ± 0.58%) MSCs) and a constitutive interferon signature linked to human disease. We demonstrate that CD317 pos MSCs induced cutaneous tissue damage when applied a skin explant model of inflammation, whereas CD317 neg MSCs had no effect. Only CD317 neg MSCs were able to suppress proliferative cycles of activated human T cells in vitro , whilst CD317 pos MSCs increased polarization towards pro-inflammatory Th1 cells and CD317 neg cell lines did not. Using an in vivo peritonitis model, we found that CD317 neg and CD317 pos MSCs suppressed leukocyte recruitment but only CD317 neg MSCs suppressed macrophage numbers. Using MSC-loaded scaffolds implanted subcutaneously in immunocompromised mice we were able to observe tissue generation and blood vessel formation with CD317 neg MSC lines, but not CD317 pos MSC lines. Our evidence is consistent with the identification of an immune stromal cell, which is likely to contribute to specific physiological and pathological functions and influence clinical outcome of therapeutic MSCs.