Ghasemzadeh Navid, Pourrajab Fatemeh, Dehghani Firoozabadi Ali, Rahnama Maryam
Department of Clinical Biochemistry and Molecular Biology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Yazd Cardiovascular Research Center, Non-Communicable Diseases Research Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Iran Biomed J. 2024 Sep 1;28(5 & 6):245-54. doi: 10.61186/ibj.4271.
Developing miRNA-mediated cell engineering introduces a novel technology for cell reprogramming and generating patient-specific tissues for therapeutic use, facilitating basic research on human adult stem cells. Furthermore, optimizing a reprogramming method without transduction minimizes the risk of tumorigenesis, especially for reprogrammed cells. This study aimed to explore the use of liposomes as vehicles for delivering miRNAs to cells, focusing on their role in regulating gene networks and facilitating nuclear reprogramming.
This study utilized cationic liposomal nanoparticles preserved under different conditions to introduce miRNAs into hMSCs. Using qPCR, the effective induction of pluripotency factors (OCT4, SOX2, and NANOG) was examined.
Results indicated that miR-302a and miR-34a regulate pluripotency by interacting with key transcription factors, including OCT4, SOX2, and NANOG. Notably, the expression pattern of OCT4 showed that lipoplexes containing miR-302a increased the expression of this gene, while in the case of miR-34a, it decreased. Additionally, the study found that pluripotency precursors can be induced by delivering liposomal microRNA (LP-miRs).
LP-miRs, as small-molecule therapeutics, can influence reprogramming/engineering and the conversion of cells into other lineages. These findings have significant implications for our understanding of the mechanisms underlying the regulation of pluripotency and may have potential applications in regenerative medicine.
开发基于微小RNA(miRNA)的细胞工程技术为细胞重编程以及生成用于治疗的患者特异性组织引入了一种新技术,有助于推动人类成体干细胞的基础研究。此外,优化无转导的重编程方法可将肿瘤发生风险降至最低,尤其是对于重编程细胞而言。本研究旨在探索使用脂质体作为将miRNA递送至细胞的载体,重点关注其在调节基因网络和促进核重编程中的作用。
本研究利用在不同条件下保存的阳离子脂质体纳米颗粒将miRNA导入人间充质干细胞(hMSCs)。使用定量聚合酶链反应(qPCR)检测多能性因子(OCT4、SOX2和NANOG)的有效诱导情况。
结果表明,miR-302a和miR-34a通过与关键转录因子(包括OCT4、SOX2和NANOG)相互作用来调节多能性。值得注意的是,OCT4的表达模式显示,含有miR-302a的脂质复合物增加了该基因的表达,而对于miR-34a,其表达则降低。此外,该研究发现,通过递送脂质体微小RNA(LP-miRs)可诱导多能性前体。
LP-miRs作为小分子疗法,可影响重编程/工程以及细胞向其他谱系的转化。这些发现对于我们理解多能性调控的潜在机制具有重要意义,并且可能在再生医学中具有潜在应用价值。