遗传修饰和预处理策略增强间充质基质细胞的功能:临床视角。

Genetic modification and preconditioning strategies to enhance functionality of mesenchymal stromal cells: a clinical perspective.

机构信息

Basic and Molecular Epidemiology of Gastroenterology Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Expert Opin Biol Ther. 2023 Jan-Jun;23(6):461-478. doi: 10.1080/14712598.2023.2205017. Epub 2023 Apr 23.

Abstract

INTRODUCTION

Mesenchymal stromal cell (MSC)-based therapy has generated great hope for the treatment of various diseases such as myocardial infarction and stroke. Unfortunately, MSC-based therapy faces major hurdles in its translation to clinical practice. To address these issues, preconditioning and genetic modification strategies have been developed. Through preconditioning, MSCs are cultured under sub-lethal conditions of environmental stresses or treated with specific drugs, biomolecules, and growth factors. Genetic modification is a procedure in which specific genetic sequences are transferred into the MSCs via viral vectors or CRISP/Cas9 in order to alter the expression of distinctive genes.

AREAS COVERED

In this article, a comprehensive review on preconditioning and gene modification inducers, mechanisms of action, and their impacts were discussed. In addition, clinical trials that used preconditioned and genetic modified MSCs are debated.

EXPERT OPINION

Numerous preclinical investigations have demonstrated that preconditioning and genetic modifications considerably enhance MSC's therapeutic capacity through improving their survival rate, antioxidant activity, growth factor secretion, immunomodulation, homing efficiency, and angiogenesis. For MSC preconditioning and genetic modification to achieve clinical translation, remarkable outcomes in clinical trials are of pivotal importance.

摘要

简介

间充质基质细胞(MSC)为治疗多种疾病,如心肌梗死和中风提供了新希望。不幸的是,MSC 疗法在向临床实践转化方面面临重大障碍。为了解决这些问题,人们已经开发出预处理和基因修饰策略。通过预处理,MSC 在亚致死的环境应激条件下培养,或用特定的药物、生物分子和生长因子处理。基因修饰是一种通过病毒载体或 CRISPR/Cas9 将特定的遗传序列转入 MSC 中,从而改变其特定基因表达的过程。

涵盖领域

本文全面综述了预处理和基因修饰诱导剂、作用机制及其影响,并讨论了使用预处理和基因修饰 MSC 的临床试验。

专家意见

大量的临床前研究表明,预处理和基因修饰可以通过提高 MSC 的存活率、抗氧化活性、生长因子分泌、免疫调节、归巢效率和血管生成能力,极大地增强 MSC 的治疗能力。为了使 MSC 的预处理和基因修饰实现临床转化,临床试验中显著的结果至关重要。

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