Senior Scientist SmartCella, Stockholms Lan, Sweden
Abstract: Osteoarthritis (OA) is characterized by progressive cartilage defect accompanied by osteophyte formation and synovial proliferation, culminating in pain, loss of mobility and even disability. Half a billion people suffer from OA globally and the prevalence is predicted to increase due to aging, obesity and injury. The current treatments for OA are merely symptomatic, and most patients ultimately require joint replacement. Thus, new treatments are required to alleviate the symptoms as well as boost cartilage regeneration to halt or reverse disease progression. Due to its anti-inflammatory and differentiational properties, mesenchymal stem/stromal cells (MSC) have been used in OA treatment, but may not be adequate for effective regeneration. Here, we generated induced human pluripotent stem cell derived MSCs (iMSC) in a homogenous and potentially scalable manner. We transfected these iMSC with modified messenger RNA (modRNA) encoding regenerative factors for the treatment of OA and assessed their regeneration effects of this iMSC-mediated modRNA delivery system (iMSC-modRNA) on articular cartilage. A surgical rat OA model with medial meniscal tear and medial collateral ligament transection in the right knee was used in the study. Joint pain was observed in this model from 1 week after operation and increased in the following 4 weeks until it reached a stable level, with significant cartilage degeneration at 6 and 10 weeks. Following a single intra-articular injection of iMSC-modRNA at 3 weeks after operation, we monitored joint pain for the duration of the study and assessed joint histology once animals were sacrificed. Compared to the untreated group, animals received iMSC-modRNA experienced symptomatic pain relief from 1 week post treatment (1wpt) until the end of the study (7wpt). The total cartilage degeneration volume showed a 15% improvement in iMSC-modRNA treated OA rats at 3wpt and enhanced further to 40% at 7wpt, indicating of cartilage regeneration in the damaged knee. In conclusion, our iMSC-mediated regenerative modRNA delivery system highlights the synergistic effect of our innovative technologies and represents significant therapeutic potential in treatment of OA.
