Global transcriptome analysis of human bone marrow stromal cells (BMSC) reveals proliferative, mobile and interactive cells that produce abundant extracellular matrix proteins, some of which may affect BMSC potency.
Cytotherapy, 2011/7;13(6):661-74.
Ren J[1], Jin P, Sabatino M, Balakumaran A, Feng J, Kuznetsov SA, Klein HG, Robey PG, Stroncek DF
Affiliations
PMID: 21250865DOI: 10.3109/14653249.2010.548379
Impact factor: 6.196
Abstract
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/β catenin signaling. Among the most highly upregulated genes were structural extracellular matrix (ECM) proteins (α5 and β5 integrin chains, fibronectin and collagen type IIIα1 and Vα1) 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.
MeSH terms
ADAM Proteins; ADAM12 Protein; Adult; Bone Marrow Cells; Cells, Cultured; Connective Tissue Growth Factor; Extracellular Matrix Proteins; Hematopoietic Stem Cells; Humans; Membrane Proteins; Mesenchymal Stem Cells; NF-E2-Related Factor 2; Oligonucleotide Array Sequence Analysis; Protein Serine-Threonine Kinases; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Stromal Cells; Transforming Growth Factor beta
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