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三维介孔支架持续释放IGF-1促进心脏干细胞迁移和增殖。

Sustained Release of IGF-1 by 3D Mesoporous Scaffolds Promoting Cardiac Stem Cell Migration and Proliferation.

作者信息

Sun Yuning, Han Xiqiong, Wang Xin, Zhu Boqian, Li Bing, Chen Zhongpu, Ma Genshan, Wan Mimi

机构信息

Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China.

National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, China.

出版信息

Cell Physiol Biochem. 2018;49(6):2358-2370. doi: 10.1159/000493836. Epub 2018 Sep 27.

Abstract

BACKGROUND/AIMS: C-kit-positive cardiac stem cells (CSCs) may have potential as a treatment for cardiovascular disease. However, the low survival rates of c-kit-positive CSCs present a major challenge during the transplantation process.

METHODS

The hierarchical structure of the 3D cell scaffold was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and N2 adsorption-desorption isotherms. Analyses of the proliferation and migration performances of the IGF-1 scaffold on c-kit-positive CSCs were conducted by experiments including QuantiT PicoGreen dsDNA and transwell assays.

RESULTS

In this study, we synthesized for the first time a novel hierarchical macro-mesoporous silica material (denoted MS15-c) in a one-pot procedure for the release of insulin-like growth factor-1 (IGF-1) and a three-dimensional (3D) cell scaffold. Both macropores and mesopores were visible in MS15-c and enabled the sustained release of IGF-1, extending its half-life and enhancing CSC proliferation and migration. Proliferation and migration were detected by QuantiT PicoGreen dsDNA and transwell assays, respectively. Moreover, an in vivo experiment was conducted to detect heart function with the addition of MS15-c. The new strategy proposed in this paper may extend the bio-applications of 3D cell scaffolds, thus permitting the sustained release of growth factors and efficient promotion of cell proliferation.

CONCLUSION

This work successfully demonstrated an effective strategy for the construction of MS15-c cell scaffolds with hierarchical macro-mesoporous structures. The macro-mesoporous structures gave cell scaffolds the ability to release a growth factor to facilitate cell growth, while the scaffold structure promoted cell proliferation.

摘要

背景/目的:c-kit阳性心脏干细胞(CSCs)可能具有治疗心血管疾病的潜力。然而,c-kit阳性CSCs的低存活率在移植过程中构成了重大挑战。

方法

通过扫描电子显微镜(SEM)、透射电子显微镜(TEM)、X射线衍射(XRD)和N2吸附-脱附等温线对三维细胞支架的层次结构进行表征。通过包括QuantiT PicoGreen双链DNA和transwell分析在内的实验,对IGF-1支架对c-kit阳性CSCs的增殖和迁移性能进行分析。

结果

在本研究中,我们首次通过一锅法合成了一种新型的具有层次结构的大孔-介孔二氧化硅材料(命名为MS15-c),用于释放胰岛素样生长因子-1(IGF-1)和一种三维(3D)细胞支架。在MS15-c中可见大孔和介孔,它们能够使IGF-1持续释放,延长其半衰期并增强CSCs的增殖和迁移。分别通过QuantiT PicoGreen双链DNA和transwell分析检测增殖和迁移情况。此外,进行了一项体内实验,以检测添加MS15-c后的心脏功能。本文提出的新策略可能会扩展3D细胞支架的生物应用,从而实现生长因子的持续释放并有效促进细胞增殖。

结论

这项工作成功证明了构建具有层次大孔-介孔结构的MS15-c细胞支架的有效策略。大孔-介孔结构赋予细胞支架释放生长因子以促进细胞生长的能力,而支架结构促进细胞增殖。

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