Pericellular collagen I coating for enhanced homing and chondrogenic differentiation of mesenchymal stem cells in direct intra-articular injection.

Pericellular collagen I coating for enhanced homing and chondrogenic differentiation of mesenchymal stem cells in direct intra-articular injection.
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细胞周 I 型胶原蛋白涂层可增强直接关节内注射间充质干细胞的归巢和软骨形成分化

DOI:
10.1186/s13287-018-0916-z
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发表时间:
2018-06-27
影响因子:
7.5
通讯作者:
Wu S
Wu S
中科院分区:
医学2区
文献类型:
--
作者:
Xia H;Liang C;Luo P;Huang J;He J;Wang Z;Cao X;Peng C;Wu S

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间充质干细胞(MSCs)的直接关节内注射(DIAI)是一种很有前景的软骨修复技术。然而,由于缺乏支架以及细胞 - 基质相互作用不佳,修复过程受到阻碍。 在这项研究中,我们在MSCs上开发了一种细胞周胶原蛋白I涂层(PCC)。在新西兰兔模型中,对MSC - PCC的归巢、软骨分化和软骨再生的整体性能进行了综合评估。首先,我们检测了PCC的形态和物理特性。其次,使用多尺度方法观察了MSC在体外对软骨切片的黏附以及在体内对软骨缺损的归巢情况。第三,检测了由MSCs聚集形成的细胞团的软骨前凝聚情况,以评估PCC的软骨诱导潜能。最后,对PCC包被的MSCs直接关节内注射后的软骨再生情况进行了宏观和组织学观察及评分。 总体而言,细胞黏附和归巢实验表明,PCC促进了MSC在软骨切片上的黏附,增强了MSC对软骨缺损的归巢和滞留。这种归巢率的提高伴随着细胞 - 细胞接触的增加。与未处理的MSCs相比,PCC包被的MSCs形成的细胞团呈现出更明显的凝聚现象。在细胞团中,细胞 - 细胞相互作用得到显著激发,诱导了凝聚标志物N - 钙黏蛋白以及随后的软骨形成标志物胶原蛋白II和聚集蛋白聚糖的表达。在直接关节内注射12周后,MSCs对软骨缺损进行了不同程度的修复。总体而言,从宏观观察、国际软骨修复协会(ICRS)评分、组织学检查以及胶原蛋白I、II和X的免疫组化染色来看,PCC显著提高了软骨再生的质量。 胶原蛋白I涂层可增强MSCs的能力和活力,为增强细胞归巢和分化提供了线索。我们的方法为干细胞治疗提供了一种新策略。 本文的网络版(10.1186/s13287 - 018 - 0916 - z)包含补充材料,授权用户可获取。
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. 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. 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. 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. The online version of this article (10.1186/s13287-018-0916-z) contains supplementary material, which is available to authorized users.
DOI: 10.1097/tp.0b013e3181a28533
发表时间: 2009-05-15
期刊: TRANSPLANTATION
影响因子: 6.2
作者:
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通讯作者: Sordi, Valeria
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DOI: 10.1074/jbc.m113.469841
发表时间: 2013-06-14
期刊: The Journal of biological chemistry
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期刊: CHEMBIOCHEM
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