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

作者：Chenchen Feng, Xuan Luo, Na He, Huitang Xia, Xiaoteng Lv, Xue Zhang, Dan Li, Fei Wang, Jiaping He, Li Zhang, Xiangming Lin, Liping Lin, Huabin Yin, Jiyin He, Jingwu Wang, Wei Cao, Richard Wang, Guangdong Zhou, Wen Wang · 发表于：Tissue Engineering Part A · 年份：2017 · DOI：10.1089/ten.tea.2017.0039 · 被引用次数：76 · 研究领域：Osteoarthritis Treatment and Mechanisms、Mesenchymal stem cell research、Periodontal Regeneration and Treatments

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 (5 × 107 cells) and low (1 × 107 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 cartilag...