细胞外胶原 I 涂层增强间充质干细胞在直接关节内注射中的归巢和软骨分化。
Pericellular collagen I coating for enhanced homing and chondrogenic differentiation of mesenchymal stem cells in direct intra-articular injection.
机构信息
Department of Orthopaedics, 3rd Xiangya Hospital, Central South University, Changsha, 410013, China.
Department of Burns and Plastic Surgery, 3rd Xiangya Hospital, Central South University, Changsha, 410013, China.
出版信息
Stem Cell Res Ther. 2018 Jun 27;9(1):174. doi: 10.1186/s13287-018-0916-z.
BACKGROUND
Direct intra-articular injection (DIAI) of mesenchymal stem cells (MSCs) is a promising technique for cartilage repair. However, the repair process was hindered by the absence of scaffold and poor cell-matrix interactions.
METHODS
In this study, we developed a pericellular collagen I coating (PCC) on MSCs. The overall performances of MSC-PCC homing, chondrogenic differentiation, and cartilage regeneration have been comprehensively evaluated in a New Zealand rabbit model. Firstly, we examined the morphology and physical characteristics of PCC. Secondly, MSC ex-vivo cartilage slice adhesion and in-vivo cartilage defect homing were observed using multiscale methods. Thirdly, the precartilage condensation of cell pellets formed by aggregation of MSCs was examined to evaluate the cartilage-inducing potential of PCC. Finally, the cartilage regeneration by DIAI of PCC-coated MSCs was observed and scored macroscopically and histologically.
RESULTS
In general, the cell adhesion and homing assay revealed that PCC facilitated MSC adhesion on cartilage slices, enhancing MSC homing and retention to cartilage defect. This increased homing ratio was accompanied by an increasing cell-cell contact. Compared with naked MSCs, the cell pellets formed by PCC-coated MSCs exhibited more evident appearance of condensation. In pellets, cell-cell interaction has been significantly stimulated, inducing the expression of condensation marker N-cadherin, and subsequent chondrogenic marker collagen II and aggrecan. By 12 weeks after DIAI, cartilage defects have been repaired by MSCs to varying degrees. Overall, PCC significantly enhances the quality of cartilage regeneration judging from macroscopic observation, ICRS score, histological examination, and collagen type I, II, and X immunohistochemical staining.
CONCLUSIONS
The capacity and viability of MSCs can be enhanced by collagen I coating, which provides cues for enhancing cell homing and differentiation. Our method provides a novel strategy for stem cell therapy.
背景
直接关节内注射（DIAI）间充质干细胞（MSCs）是一种很有前途的软骨修复技术。然而，由于缺乏支架和细胞-基质相互作用不良，修复过程受到阻碍。
方法
在这项研究中，我们开发了一种细胞外基质 I 型胶原涂层（PCC）在 MSCs 上。通过新西兰兔模型，全面评估了 MSC-PCC 归巢、软骨分化和软骨再生的整体性能。首先，我们检查了 PCC 的形态和物理特性。其次，使用多尺度方法观察 MSC 体外软骨片黏附和体内软骨缺损归巢。第三，通过聚集 MSC 形成细胞球，检查细胞球的预软骨凝聚，以评估 PCC 的软骨诱导潜力。最后，观察和评分宏观和组织学 DIAI 的 PCC 涂层 MSC 的软骨再生。
结果
一般来说，细胞黏附和归巢试验表明，PCC 促进了 MSC 在软骨片上的黏附，增强了 MSC 向软骨缺损的归巢和保留。这种归巢比例的增加伴随着细胞-细胞接触的增加。与裸 MSC 相比，PCC 涂层 MSC 形成的细胞球表现出更明显的凝聚外观。在球中，细胞-细胞相互作用得到了显著刺激，诱导了凝聚标志物 N-钙黏蛋白的表达，随后是软骨形成标志物胶原 II 和聚集蛋白。在 DIAI 后 12 周，MSC 修复了软骨缺损，程度不同。总体而言，从宏观观察、ICRS 评分、组织学检查以及 I 型、II 型和 X 型胶原免疫组织化学染色来看，PCC 显著提高了软骨再生的质量。
结论
胶原 I 涂层可以增强 MSCs 的能力和活力，为增强细胞归巢和分化提供线索。我们的方法为干细胞治疗提供了一种新的策略。
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