MMP13 and TIMP1 are functional markers for two different potential modes of action by mesenchymal stem/stromal cells when treating osteoarthritis

Ageing of human Mesenchymal stem/stromal cells (MSCs)in vitro through prolonged culture and passage results in loss of their chondrogenic potential but no reduction in their trophic repair capacity, allowing the identification of gene and protein markers of these different functions. AbstractMesenchymal stem cells (MSCs) have been investigated as a potential injectable therapy for the treatment of knee osteoarthritis, with some evidence of success in preliminary human trials. However, optimisation and scale ‐up of this therapeutic approach depends on the identification of functional markers that are linked to their mechanism of action. One possible mechanism is through their chondrogenic differentiation and direct role in neo‐cartilage synthesis. Alternatively, they could remain undifferentiated an d act through the release of trophic factors that stimulate endogenous repair processes within the joint. Here, we show that extensivein vitro ageing of bone ‐marrow‐derived human MSCs leads to loss of chondrogenesis but no reduction in trophic repair, thereby separating out the two modes of action. By integrating transcriptomic and proteomic data using Ingenuity Pathway Analysis, we found that reduced chondrogenesis with passage is linked to downreg ulation of the FOXM1 signalling pathway whilst maintenance of trophic repair is linked to CXCL12. In an attempt at developing functional markers of MSC potency, we identified loss of mRNA expression for MMP13 as correlating wit...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Regenerative Medicine Source Type: research