Development of a novel technology using mesenchymal stem cells from synovium for bone and cartilage regeneration.

关节软骨具有抗粘附特性，植入组织与邻近软骨基质的整合一直是软骨修复中的一个问题。我们已经开发了一种新的无支架三维合成组织（3DBT）组成的滑膜细胞及其合成的细胞外基质。3DST富含粘附分子，与软骨基质高度粘附，并具有高效的软骨分化潜能。在本研究中，我们探讨了3DST修复部分厚度软骨损伤的可行性。猪滑膜细胞培养时，抗坏血酸的细胞和合成的基质形成了一个坚硬的单层复合物。这种单层复合物主动收缩，以在从基底分离时形成3D组织。在4月龄猪的股骨内侧髁处造成直径6.5mm、深2mm的部分厚度缺损。将3DST植入缺损处，无需缝合。在对照组中，缺损处留空。处死动物并进行组织学评价。3个月时，对照组的缺损未修复，而植入组的缺损被修复的组织填充，并与邻近软骨平滑整合。6个月时，修复的组织保持良好的组织整合，番红O染色阳性。3DST与软骨基质高度粘附，从而安全地实现与邻近组织的良好整合。3DST在体内也表现出很强的软骨分化潜力。此外，由于无支架结构，3DST最少含有外部材料，如聚合物和动物材料。因此，3DST植入可能比传统的基于支架的细胞疗法具有长期安全性。总之，3DST技术可以为肌肉骨骼组织再生提供各种治疗干预。

Articular cartilage has anti-adhesive properties and the integration of implanted tissue to the adjacent cartilage matrix has been a concern in cartilage repair. We have developed a novel scaffold-free 3D synthetic tissue (3DBT) composed from synovial cells and their synthesized extracellular matrix. The 3DST is abundant in adhesion molecules, is highly adhesive to cartilage matrix, and has efficient chondrogenic differentiation potential. In the present study, we investigated the feasibility of the 3DST to the repair of partial-thickness chondral injury.Porcine synovial cells developed a stiff monolayer complex of the cells and the synthesized matrix when cultured with ascorbic acid. This monolayer complex actively contracts to develop a 3D-tissue when detached from the substratum. A 6.5mm diameter, 2mm deep partial-thickness defect was created at porcine medial femoral condyle of four-month-old pig. The 3DSTs were implanted in the defect without suture. In the control groups, the defect was left empty. The animals were sacrificed and evaluated histologically. At 3 months, the defect was not repaired in the control group, while the defect was filled with the repaired tissue with smooth integration to the adjacent cartilage in the implantation group. At 6 months, the repaired tissue maintained good tissue integration with positive Safranin O stainingThe 3DST is highly adhesive to the cartilage matrix and thus securely attains good integration to the adjacent tissue. The 3DST also exhibits strong chondrogenic differentiation potential in vivo. Furthermore, due to scaffold-free constitution, the 3DST minimally contains extrinsic materials such as polymers and animal materials. Thus, the 3DST implantation could potentially expect long-term safety than that of conventional scaffold-based cell therapies. Taken together, the 3DST technology could provide various therapeutic interventions for musculoskeletal tissue regeneration.