Journal
CYTOTHERAPY
Volume 13, Issue 6, Pages 661-674Publisher
ELSEVIER SCI LTD
DOI: 10.3109/14653249.2010.548379
Keywords
bone marrow stromal cells; extracellular proteins; global transcriptome analysis; potency
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Funding
- National Institute of Dental and Craniofacial Research, NIH
- Department of Transfusion Medicine, Clinical Center, NIH
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Background aims. Bone marrow stromal cells (BMSC) are being used for immune modulatory, anti-inflammatory and tissue engineering applications, but the properties responsible for these effects are not completely understood. Human BMSC were characterized to identify factors that might be responsible for their clinical effects and biomarkers for assessing their quality. Methods. Early passage BMSC prepared from marrow aspirates of seven healthy subjects were compared with three human embryonic stem cell (hESC) samples, CD34(+) cells from three healthy subjects and three fibroblast cell lines. The cells were analyzed with oligonucleotide expression microarrays with more than 35 000 probes. Results. BMSC gene expression signatures of BMSC differed from those of hematopoietic stem cells (HSC), hESC and fibroblasts. Genes upregulated in BMSC were involved with cell movement, cell-to-cell signaling and interaction and proliferation. The upregulated genes most probably belonged to pathways for integrin signaling, integrin-linked kinase (ILK) signaling, NF-E2-related factor-2 (NFR2)-mediated oxidative stress response, regulation of actin-based motility by Rho, actin cytoskeletal signaling, caveolar-mediated endocytosis, clathrin-mediated endocytosis and Wingless-type MMTV integration site (Wnt/beta) catenin signaling. Among the most highly upregulated genes were structural extracellular matrix (ECM) proteins (alpha 5 and beta 5 integrin chains, fibronectin and collagen type III alpha 1 and V alpha 1) and functional EMC proteins [ connective tissue growth factor (CTGF), transforming growth factor beta-induced protein (TGFBI) and A disintegrin and metalloproteinase (ADAM12)]. Conclusions. Global analysis of human BMSC suggests that they are mobile, metabolically active, proliferative and interactive cells that make use of integrins and integrin signaling. They produce abundant ECM proteins that may contribute to their clinical immune modulatory and anti-inflammatory effects.
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