Therapeutic efficacy of intra-articular delivery of encapsulated human mesenchymal stem cells on early stage osteoarthritis.
Therapeutic efficacy of intra-articular delivery of encapsulated human mesenchymal stem cells on early stage osteoarthritis.
复制标题
DOI：
10.22203/ecm.v037a04
复制
发表时间：
2019-01-29
影响因子：
3.1
通讯作者：
Willett NJ
中科院分区：
文献类型：
--
作者：
McKinney JM;Doan TN;Wang L;Deppen J;Reece DS;Pucha KA;Ginn S;Levit RD;Willett NJ
间充质干细胞（MSC）在骨关节炎（OA）临床前模型中代表了巨大的治疗前景，但其治疗作用机制仍存在许多问题：植入与旁分泌作用。在海藻酸钠微球中包封人MSC（hMSC）允许这些细胞的旁分泌信号传导特性独立于直接细胞植入而被分离和研究。本研究的目的是定量评估封装的hMSCs作为一种疾病修饰治疗OA的疗效，使用内侧髁撕裂（MMT）大鼠模型。据推测，封装的hMSC将通过旁分泌介导的作用对早期OA发展具有治疗作用。刘易斯大鼠接受MMT手术以诱导OA。手术后1天，大鼠接受关节内注射包封的hMSC或对照（即，盐水、空胶囊、未包封的hMSC）。在术后3周（早期OA的既定时间点），使用基于离子造影剂的微计算机断层扫描（EPIC-μCT）的平衡分配定量膝关节的显微结构变化。包封的hMSCs显着衰减MMT诱导的关节软骨肿胀和表面粗糙度的增加，并增加软骨和矿化骨赘体积。细胞包封允许分离hMSC旁分泌信号传导作用，并证明hMSC可以单独通过旁分泌信号传导对早期OA发挥软骨保护治疗作用。除了这种软骨保护作用，封装的hMSCs增强了骨赘形成的代偿性增加。后者应该被考虑在内，因为许多使用MSC治疗OA的临床试验目前正在进行中。
Mesenchymal stem cells (MSCs) represent a great therapeutic promise in pre-clinical models of osteoarthritis (OA), but many questions remain as to their therapeutic mechanism of action: engraftment versus paracrine action. Encapsulation of human MSCs (hMSCs) in sodium alginate microspheres allowed for the paracrine signaling properties of these cells to be isolated and studied independently of direct cellular engraftment. The objective of the present study was to quantitatively assess the efficacy of encapsulated hMSCs as a disease-modifying therapeutic for OA, using a medial meniscal tear (MMT) rat model. It was hypothesized that encapsulated hMSCs would have a therapeutic effect, through paracrine-mediated action, on early OA development. Lewis rats underwent MMT surgery to induce OA. 1 d post-surgery, rats received intra-articular injections of encapsulated hMSCs or controls (i.e., saline, empty capsules, non-encapsulated hMSCs). Microstructural changes in the knee joint were quantified using equilibrium partitioning of a ionic contrast agent based micro-computed tomography (EPIC-μCT) at 3 weeks post-surgery, an established time point for early OA. Encapsulated hMSCs significantly attenuated MMT-induced increases in articular cartilage swelling and surface roughness and augmented cartilaginous and mineralized osteophyte volumes. Cellular encapsulation allowed to isolate the hMSC paracrine signaling effects and demonstrated that hMSCs could exert a chondroprotective therapeutic role on early stage OA through paracrine signaling alone. In addition to this chondroprotective role, encapsulated hMSCs augmented the compensatory increases in osteophyte formation. The latter should be taken into strong consideration as many clinical trials using MSCs for OA are currently ongoing.