OSCAR (2012-2014) – Development of innovative medicines based on MSCs isolated from sinovial tissues for the treatment of bone and cartilage lesions.

QREN/SI I&DT – LISBOA-01-0202-FEDER-24765

Mesenchymal Stem Cells are multipotent stem cells that have been shown to be present in various adult tissues. Dental pulp and synovial tissues are already known for the presence of multipotent stem cells with good response to chondrogenic and osteogenic differentiation. Here we set out to isolate, culture and cryopreserve MSCs from dental pulps and synovial tissues from several medium-to-large-size animal species, in order to culture, expand, characterize and produce allogeneic MSC banks for either autologous or intra-species allogeneic treatment of bone defects and arthritic pathology. Homologous preclinical studies for the purpose of bone formation and regeneration are being performed in the porcine model. In this preliminary study, we optimised the surgical techniques needed for this research and established a protocol for mesenchymal stem cell isolation, culture and osteogenic differentiation from the porcine dental pulp (FMUL, Lisboa). The same rational is being used for isolating synovial MSCs from sheep and horses (ICETA, Univ. of Porto) and utilizing them in the treatment of osteoarthritis. Overall, the project aims at producing proof of concept to achieve therapeutic benefits to animals in the short term. Once proof of concept is achieved, we aim to use equivalent human cells in humans to bring bone and articular regeneration protocols into the clinic.

Ultrasound examination of adult horse anterior hind-limb suspensory ligament of the fetlock, showing an acute proximal desmitis. In the transverse and longitudinal ultrasonographic images there was an increased section area of the suspensory ligament in its origin demonstrating an inflammatory process. In the sub-acute phase of the inflammatory process (day 8 after the injury) MSCs from an healthy horse donor were administered intra-lesionally by ultrasound-guided injection. It was placed a compressive bandage during 24 hours, after which the animal was again placed in a paddock with reduced dimensions to limit movement and eventual trauma. One month after treatment, a physical examination and an ultrasound were performed for clinical follow-up. The animal was no longer showing ultrasound signs of inflammation or lameness.