Efficacy and Persistence of Allogeneic Adipose-Derived Mesenchymal Stem Cells Combined with Hyaluronic Acid in Osteoarthritis After Intra-articular Injection in a Sheep Model

Although a number of studies have reported efficacy of autologous adipose-derived mesenchymal stem cells (AD-MSCs) in treating osteoarthritis (OA) no reliable evidences demonstrate whether allogeneic AD-MSCs can efficiently block OA progression in a large animal model. This study explored the efficacy and survival of allogeneic AD-MSCs combined with hyaluronic acid (HA) after intra-articular (IA) injection in a sheep OA model, which were conventionally established by anterior cruciate ligament resection and medial meniscectomy. Allogeneic AD-MSCs from donor sheep at high (5x10(7) cells) and low (1x10(7) cells) doses combined with HA, HA alone, or saline alone were injected into the OA sheep at 3 and 6 weeks after surgery, respectively. Evaluations by magnetic resonance imaging (MRI), macroscopy, micro-computed tomography, and cartilage-specific staining demonstrated that AD-MSCs+HA treated groups preserved typical articular cartilage feature. Inflammatory factors from synovial fluid of AD-MSCs+HA treated groups were significantly lower than those in the HA alone group. Notably, transforming growth factor beta 1 and insulin-like growth factor 1 were detected in the supernatant of cultured AD-MSCs. In addition, labeling signals of allogeneic AD-MSCs could be detected by MRI after 14 weeks of injection and be found in synovium by histology. These results indicated that IA injection of allogeneic AD-MSCs combined with HA could efficiently block OA progression and promote cartilage regeneration and allogeneic AD-MSCs might survive at least 14 weeks after IA injection.