Epi-MSC-Score: Discern fibroblasts and mesenchymal stem cells

Mesenchymal stem cells (MSCs) raise high hopes in regenerative medicine – but reliable molecular markers to discern MSCs and fibroblasts were so far elusive. Our Epi-MSC-Score provides a simple and robust approach to support the classification of these two cell types. This facilitates quality control of your cell preparations.

Cell Culture 2 Ausschnitt

How does it work?

To identify relevant genomic regions that can discern MSCs and fibroblasts, we utilized 83 DNA methylation (DNAm) profiles from 12  studies for a training set and 107 DNAm profiles of 16 studies as validation set. Thereby, we identified two CpG dinucleotides – associated with the genes C3orf35 and CIDEC – that are rather methylated in MSCs or fibroblasts, respectively. The Epi-MSC-Score is determined as the difference of these DNAm levels: a level above 0 is indicative for MSCs. We generated pyrosequencing assays that facilitate fast and cost-effective analysis of DNAm levels at the two relevant CpGs (C3orf35 and CIDEC).

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Classification with the Epi-MSC-Score.

 

Determining the tissue of origin of MSCs

Mesenchymal stem cells (MSCs) can be isolated from various different tissues, such as bone marrow (BM) or adipose tissue (AT). There is a growing perception that MSCs isolated from these two tissues differ significantly in their differentiation potential, hematopoiesis supportive function, and immunomodulatory potential – although they look phenotypically very similar. Our Epi-Tissue-Score enables retrospective analysis of the tissue of isolation. We identified two CpG dinucleotides – associated with the genes SLC41A2 and TM4SF1 – that are either methylated in MSCs from bone marrow or adipose tissue, respectively. The Epi-Tissue-Score is determined as the difference of these DNAm levels: a level above 0 is indicative for MSCs from bone marrow. We generated pyrosequencing assays that facilitate fast and cost-effective analysis of DNAm levels at the two relevant CpGs (SLC41A2 and TM4SF1 ).

Publication:

de Almeida CD et al., Epigenetic Classification of Human Mesenchymal Stromal Cells. Stem Cell Reports 2016.

Patent application: 2016; EP16152198.4