PrimeUCX (2014-2015) – Priming of Mesenchymal Stromal Cells from the Umbilical Cord Tissue (UCX®) as a Means of Incrementing Their Therapeutic Potency for Rheumatoid Arthritis.

FCT – EXPL/DTP-FTO/0308/2013

Rheumatoid arthritis (RA) is an inflamatory autoimmune disease that primarily attacks synovial joints leading to articular destruction and functional disability. RA imparts a massive burden on health services worldwide and efforts to discover new target therapies have achieved some success. However, these new approaches are expensive and none of the currently widely used biological agents reaches long term drug-free remission. Mesenchymal Stem Cell (MSC) infusions have therapeutic potential for the treatment of inflammatory and immune-mediated adverse reactions, such as organ transplant rejection, GvHD, allergy and autoimmune diseases. ECBio has been collaborating with the Nano & Drug Delivery Systems group from iMed, Faculdade de Farmácia, Universidade de Lisboa (Nano&DDS) in demonstrating the potential of UCX® for treating inflammatory arthritic symptoms. Preliminary results from ECBio and the Nano&DDS, using a Wistar rat adjuvant model for arthritic inflammation, have  revealed a strong potential of UCX® to provoke remission of inflammatory symptoms, as measured by decreased Arthritic Index – The present project aims to 1) adopt the traditional approach of using unaltered and undifferentiated UCX® as therapeutic agents, but also 2) to use activated UCX® with enhanced anti-inflammatory properties. In order to properly validate inflammatory remission symptoms, two chronic arthritic models are being used at Nano&DDS. The results obtained in the animal models are being complemented with in vitro immunogenicity and immune-suppression assays performed at the Cellular Immunology Unit from the Institute of Molecular Medicine (CIU-IMM). In the end, we expect the project will provide both the necessary Quality data and Pre-Clinical proof-of-concept necessary to file to the regulatory authorities (EMA/INFARMED) an ATMP certification application for UCX® to treat Rheumatoid Arthritis.

Systemic delivery of UCX® cells prevent global arthritic manifestations in the Adjuvant-Induced Arthritis (AIA) model. Graphical representation of Arthritic Index (AI) variation during the time scoped by the AIA model experiment. Animals were scored at pre-selected times based on the sum of the following grades: 0 = normal paw; 1 = for each inflamed paw; 1 = tail lesion; 1 = joint rigidity or deformity; 1 = wounded paw; 1 = infected paw; 1 = necrotic paw. The sum of the parameters was calculated to a maximum AI of 9. Data is presented as mean ± SEM (n=8).