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基因传递方法在间充质干细胞治疗中的应用:提高效率和特异性的策略。

Gene Delivery Approaches for Mesenchymal Stem Cell Therapy: Strategies to Increase Efficiency and Specificity.

机构信息

CSIR-Center for Cellular and Molecular Biology, Medical Biotechnology Complex, Uppal Road, Hyderabad, Telangana, 500007, India.

MNR Dental College and Hospital, Fasalwadi, Sangareddy, Telangana, 500076, India.

出版信息

Stem Cell Rev Rep. 2017 Dec;13(6):725-740. doi: 10.1007/s12015-017-9760-2.

Abstract

A significant number of clinical trials have been undertaken to explore the use of mesenchymal stem cells (MSCs) for the treatment of several diseases such as Crohn's disease, diabetes, bone defects, myocardial infarction, stroke etc., Due to their efficiency in homing to the tissue injury sites, their differentiation potential, the capability to secrete a large amount of trophic factors and their immunomodulatory effects, MSCs are becoming increasingly popular and expected to be one of the promising therapeutic approaches. However, challenges associated with the isolation of pure MSC populations, their culture and expansion, specific phenotypic characterization, multi-potential differentiation and challenges of efficient transplantation limit their usage. The current strategies of cell-based therapies emphasize introducing beneficial genes, which will improve the therapeutic ability of MSCs and have better homing efficiency. The continuous improvement in gene transfer technologies has broad implications in stem cell biology. Although viral vectors are efficient vehicles for gene delivery, construction of viral vectors with desired genes, their safety and immunogenicity limit their use in clinical applications. We review current gene delivery approaches, including viral and plasmid vectors, for transfecting MSC with beneficial genes. The review also discusses the use of a few emerging technologies that could be used to improve the transfer/induction of desirable genes for cell therapy.

摘要

大量临床试验已经开展,旨在探索间充质干细胞(MSCs)在治疗多种疾病中的应用,如克罗恩病、糖尿病、骨缺损、心肌梗死、中风等。由于 MSCs 具有向组织损伤部位归巢的能力、分化潜能、分泌大量营养因子的能力和免疫调节作用,因此它们越来越受到关注,并有望成为有前途的治疗方法之一。然而,与 MSC 纯培养物的分离、培养和扩增、特定表型特征、多能分化以及高效移植相关的挑战限制了其应用。目前的基于细胞的治疗策略强调引入有益基因,这将提高 MSC 的治疗能力,并具有更好的归巢效率。基因转移技术的不断改进对干细胞生物学具有广泛的影响。虽然病毒载体是高效的基因传递载体,但构建具有所需基因的病毒载体,其安全性和免疫原性限制了它们在临床应用中的使用。我们综述了目前用于将有益基因转染 MSC 的基因传递方法,包括病毒和质粒载体。本文还讨论了一些新兴技术的应用,这些技术可能用于提高细胞治疗中所需基因的转移/诱导效率。

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