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利用 M2 巨噬细胞极化在小肠黏膜下层中增强肌腱衍生干细胞的肌腱修复作用。

Enhancement of Tendon Repair Using Tendon-Derived Stem Cells in Small Intestinal Submucosa via M2 Macrophage Polarization.

机构信息

Department of Orthopaedic Surgery, The Affiliated Hospital of Medical School, Ningbo University, Ningbo 315020, China.

Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China.

出版信息

Cells. 2022 Sep 5;11(17):2770. doi: 10.3390/cells11172770.

DOI:10.3390/cells11172770
PMID:36078178
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9454771/
Abstract

(1) Background: Reconstruction of Achilles tendon defects and prevention of postoperative tendon adhesions were two serious clinical problems. In the treatment of Achilles tendon defects, decellularized matrix materials and mesenchymal stem cells (MSCs) were thought to address both problems. (2) Methods: In vitro, cell adhesion, proliferation, and tenogenic differentiation of tendon-derived stem cells (TDSCs) on small intestinal submucosa (SIS) were evaluated. RAW264.7 was induced by culture medium of TDSCs and TDSCs-SIS scaffold groups. A rat Achilles tendon defect model was used to assess effects on tendon regeneration and antiadhesion in vivo. (3) Results: SIS scaffold facilitated cell adhesion and tenogenic differentiation of TDSCs, while SIS hydrogel coating promoted proliferation of TDSCs. The expression of TGF-β and ARG-1 in the TDSCs-SIS scaffold group were higher than that in the TDSCs group on day 3 and 7. In vivo, the tendon regeneration and antiadhesion capacity of the implanted TDSCs-SIS scaffold was significantly enhanced. The expression of CD163 was significantly highest in the TDSCs-SIS scaffold group; meanwhile, the expression of CD68 decreased more significantly in the TDSCs-SIS scaffold group than the other two groups. (4) Conclusion: This study showed that biologically prepared SIS scaffolds synergistically promote tendon regeneration with TDSCs and achieve antiadhesion through M2 polarization of macrophages.

摘要

(1) 背景:跟腱缺损的重建和术后肌腱粘连的预防是两个严重的临床问题。在跟腱缺损的治疗中,去细胞基质材料和间充质干细胞(MSCs)被认为可以同时解决这两个问题。

(2) 方法:在体外,评估肌腱源性干细胞(TDSCs)在小肠黏膜下层(SIS)上的细胞黏附、增殖和肌腱分化。通过TDSCs 和 TDSCs-SIS 支架组的培养培养基诱导 RAW264.7。使用大鼠跟腱缺损模型评估体内对肌腱再生和抗粘连的影响。

(3) 结果:SIS 支架促进了 TDSCs 的细胞黏附和肌腱分化,而 SIS 水凝胶涂层促进了 TDSCs 的增殖。TDSCs-SIS 支架组在第 3 天和第 7 天 TGF-β和 ARG-1 的表达均高于 TDSCs 组。体内,植入的 TDSCs-SIS 支架明显增强了肌腱的再生和抗粘连能力。CD163 在 TDSCs-SIS 支架组中的表达最高;同时,与其他两组相比,TDSCs-SIS 支架组中 CD68 的表达下降更为显著。

(4) 结论:本研究表明,生物制备的 SIS 支架与 TDSCs 协同促进肌腱再生,并通过巨噬细胞的 M2 极化实现抗粘连。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/451d/9454771/d0497b72dbba/cells-11-02770-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/451d/9454771/81afcf114cba/cells-11-02770-g005.jpg
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