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miR-106b-5p表达在小鼠精原干细胞形成畸胎瘤及三个胚层过程中产生类诱导多能干细胞的作用。

The Effect of miR-106b-5p Expression in The Production of iPS-Like Cells from Mice SSCs during The Formation of Teratoma and The Three Embryonic Layers.

作者信息

Hasani Fard Amir Hossein, Kamalipour Fatemeh, Mazaheri Zohreh, Hosseini Seyed Jalil

机构信息

Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

出版信息

Cell J. 2022 Aug 28;24(8):442-448. doi: 10.22074/cellj.2022.8147.

Abstract

Objective: According to the mounting data, microRNAs (miRNAs) may play a key role in reprogramming. miR-106b
is considered as an enhancer in reprogramming efficiency. Based on induced pluripotent stem cells (iPSCs), cell treatments have a huge amount of potential. One of the main concerns about using iPSCs in therapeutic settings is the possibility of tumor formation. It is hypothesized that a procedure that can reprogram cells with less genetic manipulation reduces the possibility of tumorigenicity.
Materials and Methods: In this experimental study, miR-106b-5p transduced by pLV-miRNA vector into mice isolated spermatogonial stem cells (SSCs) to achieve iPS-like cells. Then the transduced cells were cultured in specific conditions to study the formation of three germ layers. The tumorigenicity of these iPS-like cells was investigated by transplantation into male BALB/C mice.
Results: We show that SSCs can be successfully reprogrammed into induced iPS-like cells by pLV-miRNA vector to transduce the hsa-mir-106b-5p into SSCs and generating osteogenic, neural and hepatoblast lineage cells in vitro as a result of pluripotency. Although these iPS-like cells are pluripotent, they cannot form palpable tumors in vivo.
Conclusion: These results demonstrate that infection of hsa-mir-106b-5p into SSCs can reprogram them into iPSCs
and advanced germ cell lineages without tumorigenicity. Also, a novel approach for studying the generation of iPSCs
and the application of iPS or iPS-like cells in regenerative medicine is presented.

摘要

目的:根据越来越多的数据,微小RNA(miRNA)可能在重编程中起关键作用。miR-106b被认为是重编程效率的增强子。基于诱导多能干细胞(iPSC),细胞治疗具有巨大的潜力。在治疗环境中使用iPSC的主要担忧之一是肿瘤形成的可能性。据推测,一种能够以较少基因操作对细胞进行重编程的方法可降低致瘤性的可能性。

材料和方法:在本实验研究中,通过pLV-miRNA载体将miR-106b-5p转导到从小鼠分离的精原干细胞(SSC)中以获得诱导多能干细胞样细胞。然后将转导后的细胞在特定条件下培养以研究三个胚层的形成。通过将这些诱导多能干细胞样细胞移植到雄性BALB/C小鼠中来研究其致瘤性。

结果:我们表明,通过pLV-miRNA载体将hsa-mir-106b-5p转导到SSC中,可成功将SSC重编程为诱导多能干细胞样细胞,并由于多能性在体外产生成骨、神经和肝母细胞谱系细胞。虽然这些诱导多能干细胞样细胞具有多能性,但它们在体内不能形成可触及的肿瘤。

结论:这些结果表明,将hsa-mir-106b-5p导入SSC可将其重编程为诱导多能干细胞和高级生殖细胞谱系,且无致瘤性。此外,还提出了一种研究诱导多能干细胞生成以及诱导多能干细胞或诱导多能干细胞样细胞在再生医学中应用的新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85f6/9468720/a01096acd210/Cell-J-24-442-g01.jpg

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