The articular cartilage is a tissue affected by different joint diseases such as rheumatoid arthritis and osteoarthritis and has a very limited regeneration capacity. Mesenchymal stem cells have demonstrated good plasticity, similar to embryonic stem cells but without ethical complications. For this reason are attractive sources of cells for regenerating cartilage. Understanding the mechanism of chondrogenesis (cartilage generation) is required. MicroRNAs are endogenous molecules that regulate gene expression. The main objective of the project is studying the microRNA profile of mesenchymal stem cells taken from umbilical cord, and certain subpopulations with varying chondrogenic potential, comparing the results. The donor partner, will provide experience in the study of microRNAs and genomic techniques. Project promoter will provide extensive experience in proteomics (Iarge-scale proteomics), in addition to providing a new source of cells (umbilical card) and subpopulations separated for comparison. The main beneficiaries of the project will be the scientific community and patients at all levels.
Summary of project results
The aim of this study, performed by the grantee within his predoctoral work, was to silence the lL1β receptor (ll1R1) in human articular chondrocytes and human mesenchymal stem cells in order to determine its effect on the inflammatory response and the chondrogenic redifferentiation potential of cells after stimulation with recombinant IL1β (rIL 1β). MicroRNAs (miRNAs) play an important role in the regulation of chondrogenesis of mesenchymal stem cells, but their expression and mechanism still remain unknown. Chondrogenesis induced by tissue-engineering methods is essential to treating cartilage-related diseases, so, a deeper understanding about miRNAs regulation is needed. In the one hand we found some very promising results knocking down the IL1 receptor IL1R1 (using Crispr-Cas9 technology) in chondrocytes and we are very interested in this right now. We found that cells with the knockout are “protected” against the action of proinflammatory molecules like TNF and IL1, presented in damaged and OA joints (which have an inhibitory effect on chondrogenesis). In the other hand the grantee found two microRNAs (microRNA 21 and microRNA 201), and one microRNA-binding protein called Lin28 that could be important for therapeutic targets. MicroRNA21 is upregulated in osteoarthritis and overexpression attenuate the process of chondrogenesis. Partners are investigating the effect of knockdown this gene to improve a better chondrogenesis. MicroRNA201 plays a wide spectrum of roles comprising mitochondrial metabolisim, angiogenesis, DNA repair and cell survival. Partners are testing the effect of the overexpression in chondrogenic systems. Lin-28 plays a role in developing pluripotency and metabolism. Partners are testing the effect of the overexpression in our chondrogenic systems too. Partners hope to continue with this experiment in Spain, keeping the collaboration with Brinchmann’s group. Grantee attended internal weekly seminars and bigger seminars in University of Oslo and presented his work in such forum. A couple of scientific papers are in preparation.
Summary of bilateral results
Working at the host institution was very important for the grantee in order to learn and work at the laboratories. Brinchmann laboratory provided all physical media, reagents, equipments, workspace etc., as well as the tutelage and assistance of every kind to the grantee at every time. At the closure of the NILS funding, they still are performing some experiments. They are planning a meeting between the two laboratories in Spain, in order to discuss future cooperation plans, among them, the grantee expects to come back to Norway during his postdoc stage.