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软骨形成过程中基于胶原蛋白的支架对间充质干细胞(MSCs)免疫调节因子分泌的调控

Regulation of the secretion of immunoregulatory factors of mesenchymal stem cells (MSCs) by collagen-based scaffolds during chondrogenesis.

作者信息

Yang Jingyu, Chen Xuening, Yuan Tun, Yang Xiao, Fan Yujiang, Zhang Xingdong

机构信息

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China.

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China.

出版信息

Mater Sci Eng C Mater Biol Appl. 2017 Jan 1;70(Pt 2):983-991. doi: 10.1016/j.msec.2016.04.096. Epub 2016 Apr 28.

Abstract

In the latest decade, mesenchymal stem cells (MSCs) have wildly considered as a source of seeded cells in tissue engineering, not only because of its multi-differentiation potentials, but also due to its immunoregulation ability. The main immunoregulatory features of MSCs could be divided into low self-immunogenicity and secretion of soluble factors. In this study, we explored how scaffold structures modulated the secretion of soluble immunoregulatory factors in MSCs under an allogeneic cartilage tissue engineering background. MSCs were seeded in four different collagen-based scaffolds. Their proliferation, differentiation, and secretion of various soluble factors associated with the immunosuppressive effects were evaluated. In this study, qRT-PCR, ELISA and immunoregulation results showed a great variability of the factor secretion by MSCs seeded in scaffolds with different structures. Compared with two-dimensional (2D) monolayer culture condition, three-dimensional (3D) groups (hydrogels and sponge) could effectively promote the mRNA expression and the protein production of soluble immune-related factors. Also, the supernatants collected from 3D groups obviously showed inhibition on allogeneic lymphocyte activating. These results suggested that scaffold structures might modulate MSCs' secretion of soluble immunoregulatory factors, and our study might enlighten the scaffold designs for desired tissue regeneration to control the host immune rejection through immune-regulation reaction.

摘要

在最近十年中,间充质干细胞(MSCs)被广泛认为是组织工程中种子细胞的来源,这不仅是因为其多向分化潜能,还因其免疫调节能力。MSCs的主要免疫调节特性可分为低自身免疫原性和可溶性因子的分泌。在本研究中,我们探讨了在同种异体软骨组织工程背景下,支架结构如何调节MSCs中可溶性免疫调节因子的分泌。将MSCs接种在四种不同的基于胶原蛋白的支架中。评估了它们的增殖、分化以及与免疫抑制作用相关的各种可溶性因子的分泌。在本研究中,qRT-PCR、ELISA和免疫调节结果显示,接种在不同结构支架中的MSCs分泌因子存在很大差异。与二维(2D)单层培养条件相比,三维(3D)组(水凝胶和海绵)可有效促进可溶性免疫相关因子的mRNA表达和蛋白质产生。此外,从3D组收集的上清液明显显示出对同种异体淋巴细胞活化的抑制作用。这些结果表明,支架结构可能调节MSCs可溶性免疫调节因子的分泌,我们的研究可能为通过免疫调节反应控制宿主免疫排斥以实现所需组织再生的支架设计提供启示。

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