Open AccessTranscriptional profile of native CD271+ multipotential stromal cells: Evidence for multiple fates, with prominent osteogenic and Wnt pathway signaling activity
Author(s) -
Churchman Sarah M.,
Ponchel Frederique,
Boxall Sally A.,
Cuthbert Richard,
Kouroupis Dimitrios,
Roshdy Tarek,
Giannoudis Peter V.,
Emery Paul,
McGonagle Dennis,
Jones Elena A.
Publication year - 2012
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.34434
Subject(s) - stromal cell , mesenchymal stem cell , biology , wnt signaling pathway , microbiology and biotechnology , haematopoiesis , adipogenesis , bone marrow , stem cell , cancer research , immunology , signal transduction
Objective Controversy surrounds the identity and functionality of rare bone marrow–derived multipotential stromal cells (BM‐MSCs), including their differentiation capabilities, their relationship to pericytes and hematopoiesis‐supporting stromal cells, and the relevance of their culture‐expanded progeny in studies of skeletal biology and development of cell‐based therapies. The aim of this study was to clarify the nature of candidate BM‐MSCs by profiling transcripts that reflect different aspects of their putative functions in vivo. Methods Rare, sorted BM‐derived CD45 −/low CD271 bright (CD271) cells were analyzed using 96‐gene expression arrays focused on transcripts relevant to mesenchymal‐lineage differentiation (toward bone, cartilage, fat, or muscle), hematopoietic and stromal support, and molecules critical to skeletal homeostasis. These cells were compared to matched CD45+ CD271− hematopoietic‐lineage cells, culture‐expanded MSCs, and skin fibroblasts. When feasible, transcription was validated using flow cytometry. Results CD271 cells had a transcriptional profile consistent with the multiple fates of in vivo MSCs, evident from the observed simultaneous expression of osteogenic, adipogenic, pericytic, and hematopoiesis‐supporting genes (e.g., SP7 [osterix], FABP4 [fatty acid binding protein 4], ANGPT1 [angiopoietin 1], and CXCL12 [stromal cell–derived factor 1], respectively). Compared to culture‐expanded MSCs and fibroblasts, CD271 cells exhibited greater transcriptional activity, particularly with respect to Wnt‐related genes (>1,000‐fold increased expression of FRZB [secreted frizzled‐related protein 3] and WIF1 [Wnt inhibitory factor 1]). A number of transcripts were identified as novel markers of MSCs. Conclusion The native, BM‐derived in vivo MSC population is endowed with a gene signature that is compatible with multiple functions, reflecting the topographic bone niche of these cells, and their signature is significantly different from that of culture‐expanded MSCs. This indicates that studies of the biologic functions of MSCs in musculoskeletal diseases, including osteoporosis and osteoarthritis, should focus on in vivo MSCs, rather than their culture‐adapted progeny.