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生物工程工具阐明和控制移植干细胞的命运。

Bioengineering tools to elucidate and control the fate of transplanted stem cells.

机构信息

*Department of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.

†Division of Biomedical Engineering, Department of Medicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, U.S.A.

出版信息

Biochem Soc Trans. 2014 Jun;42(3):679-87. doi: 10.1042/BST20130276.

Abstract

For the last decade, stem cell therapies have demonstrated enormous potential for solving some of the most tragic illnesses, diseases and tissue defects worldwide. Currently, more than 1300 clinical trials use stem cell therapy to solve a spectrum of cardiovascular, neurodegenerative and autoimmune diseases (http://www.clinicaltrials.gov, Jan 2014, search term: stem cell therapy; only currently recruiting and completed studies are included in the search). However, the efficacy of stem cell transplantation in patients has not been well established, and recent clinical trials have produced mixed results. We attribute this lack of efficacy in part to an incomplete understanding of the fate of stem cells following transplantation and the lack of control over cell fate, especially cell-homing and therapeutic functions. In the present review, we present two of our recently developed technologies that aim to address the above-mentioned bottlenecks in stem cell therapy specifically in the areas of MSCs (mesenchymal stem cells): (i) aptamer-based cell-surface sensors to study cellular microenvironments, and (ii) mRNA engineering technology to enhance the homing and immunomodulatory efficacy of transplanted stem cells. The first engineering strategy aims to elucidate the basic cellular signalling that occurs in the microenvironment of transplanted stem cells in real time. The second technique involves a simple mRNA transfection that improves the homing and anti-inflammatory capability of MSCs. Although we have specifically applied these engineering techniques to MSCs, these strategies can be incorporated for almost any cell type to determine and control the fate of transplanted stem cells.

摘要

在过去的十年中,干细胞疗法已经显示出了巨大的潜力,可以解决全球范围内一些最严重的疾病、病症和组织缺陷。目前,有超过 1300 项临床试验使用干细胞疗法来解决一系列心血管、神经退行性和自身免疫性疾病(http://www.clinicaltrials.gov,2014 年 1 月,搜索词:干细胞疗法;仅包括目前正在招募和已完成的研究)。然而,干细胞移植在患者中的疗效尚未得到很好的证实,最近的临床试验结果喜忧参半。我们认为这种疗效的缺乏部分是由于对移植后干细胞命运的不完全了解以及对细胞命运的缺乏控制,特别是细胞归巢和治疗功能。在本综述中,我们介绍了我们最近开发的两种技术,旨在专门针对间充质干细胞(MSCs)的干细胞治疗中的上述瓶颈问题:(i)基于适体的细胞表面传感器来研究细胞微环境,以及(ii)mRNA 工程技术来增强移植干细胞的归巢和免疫调节功效。第一种工程策略旨在实时阐明移植干细胞微环境中发生的基本细胞信号。第二种技术涉及一种简单的 mRNA 转染,可提高 MSCs 的归巢和抗炎能力。尽管我们已经专门将这些工程技术应用于 MSCs,但这些策略可以应用于几乎任何类型的细胞,以确定和控制移植干细胞的命运。

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