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

TY - JOUR

T1 - Multiparameter Analysis of Human Bone Marrow Stromal Cells Identifies Distinct Immunomodulatory and Differentiation-Competent Subtypes

AU - James, Sally

AU - Fox, James

AU - Afsari, Farinaz

AU - Lee, Jennifer

AU - Clough, Sally

AU - Knight, Charlotte

AU - Ashmore, James

AU - Ashton, Peter

AU - Preham, Olivier

AU - Hoogduijn, Martin

AU - Ponzoni, Raquel De Almeida Rocha

AU - Hancock, Y

AU - Coles, Mark

AU - Genever, Paul

N1 - © 2015 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

PY - 2015/6/9

Y1 - 2015/6/9

N2 - 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 ∼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.

AB - 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 ∼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.

U2 - 10.1016/j.stemcr.2015.05.005

DO - 10.1016/j.stemcr.2015.05.005

M3 - Article

C2 - 26070611

SN - 2213-6711

VL - 4

SP - 1004

EP - 1015

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 6

ER -