Multiparameter Analysis of Human Bone Marrow Stromal Cells Identifies Distinct Immunomodulatory and Differentiation-Competent Subtypes

S James, J Fox, F Afsari, J Lee, S Clough, C Knight, J Ashmore, P Ashton, O Preham, Martin Hoogduijn, RDR Ponzoni, Y Hancock, M Coles, P Genever

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Abstract

Bone marrow stromal cells (BMSCs, also called bone-marrow-derived mesenchymal stromal cells) provide hematopoietic support and immunoregulation and contain a stem cell fraction capable of skeletogenic differentiation. We used immortalized human BMSC clonal lines for multi-level analysis of functional markers for BMSC subsets. All clones expressed typical BMSC cell-surface antigens; however, clones with trilineage differentiation capacity exhibited enhanced vascular interaction gene sets, whereas non-differentiating clones were uniquely CD317 positive with significantly enriched immunomodulatory transcriptional networks and high IL-7 production. IL-7 lineage tracing and CD317 immunolocalization confirmed the existence of a rare non-differentiating BMSC subtype, distinct from Cxcl12-DsRed(+) perivascular stromal cells in vivo. Colony-forming CD317(+) IL-7(hi) cells, identified at similar to 1%-3% frequency in heterogeneous human BMSC fractions, were found to have the same biomolecular profile as non-differentiating BMSC clones using Raman spectroscopy. Distinct functional identities can be assigned to BMSC subpopulations, which are likely to have specific roles in immune control, lymphopoiesis, and bone homeostasis.
Original languageUndefined/Unknown
Pages (from-to)1004-1015
Number of pages12
JournalStem Cell Reports
Volume4
Issue number6
DOIs
Publication statusPublished - 2015

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