Journal
STEM CELL REVIEWS AND REPORTS
Volume 10, Issue 3, Pages 376-388Publisher
SPRINGER
DOI: 10.1007/s12015-014-9498-z
Keywords
MSC; Heterogeneity; LBP; TGF beta 1; TLR
Funding
- Leona M. and Harry B. Helmsley Charitable Trust
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The outstanding heterogeneity of stem cell populations is a major obstacle on the way to their clinical application. It is therefore paramount to identify the molecular mechanisms that underlay this heterogeneity. Individually derived bone marrow mesenchymal stromal cells (MSCs) preparations, studied here, diverged markedly in various properties, despite of being all tripotent in their differentiation potential. Microarray analysis showed that MSC diversity is evident also in highly variable gene expression patterns. Differentially expressed genes were significantly enriched in toll-like receptors (TLRs) and differentiation pathways. Marked differences were observed in LPS binding protein (LBP) and transforming growth factor (TGF) beta 1 expression. These differences correlated with MSC functionality. Therefore, the possible contribution of these molecules to MSC diversity was examined. In the TLR signaling pathway, LBP levels predicted the ability of specific MSCs to secrete interleukin (IL)-6 in response to LPS. A relatively higher expression of TGF beta 1 endowed MSCs with a capacity to respond to IL-1 beta by reduced osteogenic differentiation. This study thus demonstratesmajor diversity withinMSC isolates, which appears early on following derivation and persists following long-term culture. MSC heterogeneity results from highly variable transcriptome. Differential expression of LBP and TGF beta 1, along with other genes, in different MSC preparations, produces the variable responses to external stimuli.
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