کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2093542 | 1081965 | 2015 | 12 صفحه PDF | دانلود رایگان |
• Immortalized BMSC clones were generated for in-depth functional and biophysical analysis
• Distinct differentiation-competent and incompetent BMSC subsets are defined
• Trilineage-competent BMSC clones exhibit enhanced vascular interaction gene sets
• A non-differentiating, “immune-primed,” CD317+/IL-7hi BMSC subset was identified in vivo
SummaryBone 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-7hi cells, identified at ∼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.
Journal: - Volume 4, Issue 6, 9 June 2015, Pages 1004–1015