1 NWO Stem Cure, LLC, Findlay, OH, USA.
2 Northwest Ohio Orthopedics and Sports Medicine, Findlay, OH, USA.
Cell Transplant. 2017 Aug;26(8):1405-1417. doi: 10.1177/0963689717720278.
Osteoarthritis (OA) is an inflammatory joint disease characterized by degeneration of articular cartilage within synovial joints. An estimated 27 million Americans suffer from OA, and the population is expected to reach 67 million in the United States by 2030. Thus, it is urgent to find an effective treatment for OA. Traditional OA treatments have no disease-modifying effect, while regenerative OA therapies such as autologous chondrocyte implantation show some promise. Nonetheless, current regenerative therapies do not overcome synovial inflammation that suppresses the differentiation of mesenchymal stem cells (MSCs) to chondrocytes and the expression of type II collagen, the major constituent of functional cartilage. We discovered a synergistic combination that overcame synovial inflammation to form type II collagen-producing chondrocytes. The combination consists of peroxisome proliferator-activated receptor (PPAR) δ agonist, human bone marrow (hBM)-derived MSCs, and hyaluronic acid (HA) gel. Interestingly, those individual components showed their own strong enhancing effects on chondrogenesis. GW0742, a PPAR-δ agonist, greatly enhanced MSC chondrogenesis and the expression of type II collagen and glycosaminoglycan (GAG) in hBM-MSC-derived chondrocytes. GW0742 also increased the expression of transforming growth factor β that enhances chondrogenesis and suppresses cartilage fibrillation, ossification, and inflammation. HA gel also increased MSC chondrogenesis and GAG production. However, neither GW0742 nor HA gel could enhance the formation of type II collagen-producing chondrocytes from hBM-MSCs within human OA synovial fluid. Our data demonstrated that the combination of hBM-MSCs, PPAR-δ agonist, and HA gel significantly enhanced the formation of type II collagen-producing chondrocytes within OA synovial fluid from 3 different donors. In other words, the novel combination of PPAR-δ agonist, hBM-MSCs, and HA gel can overcome synovial inflammation to form type II collagen cartilage within human OA synovial fluid. This novel articularly injectable formula could improve OA treatment in the future clinical application.
骨关节炎（OA）是一种炎症性关节疾病，其特征是滑膜关节内关节软骨退化。估计有 2700 万美国人患有 OA，到 2030 年，美国的患者人数预计将达到 6700 万。因此，迫切需要找到一种有效的 OA 治疗方法。传统的 OA 治疗方法没有疾病修饰作用，而自体软骨细胞移植等再生 OA 疗法则显示出一定的前景。尽管如此，目前的再生疗法并不能克服抑制间充质干细胞（MSCs）向软骨细胞分化和 II 型胶原表达的滑膜炎症，II 型胶原是功能性软骨的主要成分。我们发现了一种协同组合，可以克服滑膜炎症，形成产生 II 型胶原的软骨细胞。该组合由过氧化物酶体增殖物激活受体（PPAR）δ 激动剂、人骨髓（hBM）来源的 MSC 和透明质酸（HA）凝胶组成。有趣的是，这些单个成分本身就表现出很强的增强软骨形成的作用。PPAR-δ 激动剂 GW0742 极大地增强了 MSC 的软骨形成和 hBM-MSC 来源的软骨细胞中 II 型胶原和糖胺聚糖（GAG）的表达。GW0742 还增加了转化生长因子β的表达，该因子增强软骨形成并抑制软骨纤维化、骨化和炎症。HA 凝胶也增加了 MSC 的软骨形成和 GAG 产生。然而，GW0742 或 HA 凝胶都不能增强 hBM-MSC 在人 OA 滑膜液中形成产生 II 型胶原的软骨细胞。我们的数据表明，hBM-MSC、PPAR-δ 激动剂和 HA 凝胶的组合显著增强了来自 3 个不同供体的 OA 滑膜液中产生 II 型胶原的软骨细胞的形成。换句话说，PPAR-δ 激动剂、hBM-MSC 和 HA 凝胶的新型组合可以克服滑膜炎症，在人 OA 滑膜液中形成 II 型胶原软骨。这种新型的关节内可注射配方可在未来的临床应用中改善 OA 的治疗效果。
