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Published on: May 21, 2013
Osteoarthritis Bone Marrow MSCs Retain Regenerative Competence and Chemokine Responsiveness for Drug-Based In Situ
Julia Sonnleitner1, Katja Gulich1, Axel Pruss2
1Tissue Engineering Laboratory, Department for Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, Berlin, 10117, Germany, charite.de.
Background:
Mesenchymal stromal cells (MSCs) support tissue repair in osteoarthritis (OA), with migration to damaged tissue being a key strategy in in situ tissue engineering. Their regenerative potential depends on factors such as differentiation, level of senescence, and responsiveness to signaling molecules. However, previous findings on these properties of OA MSCs remain inconclusive. This study integrates multiple aspects and tests feasibility using a well-characterized chemoattractant.
Methods And Results:
MSCs from non-OA donor (ND) and OA donor were characterized for their trilineage differentiation potential as well as for their senescence level by (immune-) histochemistry, RT-qPCR, microarray analysis, and a bead-based immunoassay for cell culture supernatants. No difference in differentiation and senescence level was observed, the latter being indicated by a similar activity of β-Galactosidase (β-gal), gene expression profiles of cyclin-dependent kinase (CDKN) inhibitor 2A (CDKN2A), CDKN inhibitor 1A (CDKN1A), sirtuin 1 (SIRT1), and matrix metallopeptidase 1 (MMP1), as well as secreted cytokines. Chemokine receptors in OA MSCs were detected using immunohistochemistry and RT-qPCR. Expression of CCR1-CCR7, CCR9, and CXCR1-CXCR6 in OA MSCs was confirmed on gene and protein levels. Both OA and ND MSCs migrated toward 1000 nM CCL25, as evaluated via a Boyden chamber assay. Subsequent genome-wide microarray analysis of OA MSCs after treatment with 1000 nM CCL25 corroborated its influence on migration, proliferation, apoptosis, and differentiation as defined by Gene Ontology terms (GO terms). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis confirmed this broad impact and emphasized the role of cytokine-cytokine-receptor interaction and metabolic pathways.
Conclusion:
Our data indicate that OA MSCs retain their differentiation potential and do not exhibit an increased senescent phenotype. Their chemokine receptor profile is conducive of migration, and both OA and ND MSCs respond to CCL25, highlighting the potential of OA MSCs for directed in situ repair.
