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单磷酰脂质A与视黄酸组合可增加人脐带间充质基质细胞在羊脱细胞睾丸支架中的生殖细胞分化标志物表达。

Monophosphoryl Lipid A and Retinoic Acid Combinations Increased Germ Cell Differentiation Markers Expression in Human Umbilical Cord-derived Mesenchymal Stromal Cells in an Ovine Acellular Testis Scaffold.

作者信息

Shojaeian Ali, Mehri-Ghahfarrokhi Ameneh, Banitalebi-Dehkordi Mehdi

机构信息

Department of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

出版信息

Int J Mol Cell Med. 2020 Fall;9(4):288-296. doi: 10.22088/IJMCM.BUMS.9.4.288. Epub 2021 Jan 27.

Abstract

Infertility is known as one of the most common problems among couples. In this regard, generation of male germ cells from adult stem ones are among the current promising priorities of researchers. Mesenchymal stromal cells (MSCs) were previously induced to differentiate into germ-like progenitors . Monophosphoryl lipid A (MPLA) is a detoxified derivative of lipopolysaccharides (LPS) that lacks many of the endotoxic properties of LPS. Our present study aimed to investigate the expression of migration genes (, , , , and ), and differentiation markers during human umbilical mesenchymal stromal cells (hUMSCs) culture in the presence of retinoic acid (RA) and MPLA-treated acellular testis. Accordingly, the high expression levels of deleted in azoospermia-like (DAZL), piwi-like RNA-mediated gene silencing 2 (PIWIL2) transcripts as well as protein were consequently observed in treated hUMSCs. It was concluded that combination treatment (i.e., MPLA/RA) had more prominent results than each of the treatments alone, even though MPLA and RA could be regarded as inducer of migration and differentiation, respectively. Ultimately, it was suggested to introduce the use of combination treatment as a more effective strategy to improve therapies in regenerative medicine.

摘要

不孕症是夫妻中最常见的问题之一。在这方面,从成体干细胞生成雄性生殖细胞是研究人员当前有前景的优先事项之一。间充质基质细胞(MSCs)先前已被诱导分化为类生殖祖细胞。单磷酰脂质A(MPLA)是脂多糖(LPS)的一种解毒衍生物,缺乏LPS的许多内毒素特性。我们目前的研究旨在调查在视黄酸(RA)和MPLA处理的无细胞睾丸存在下,人脐间充质基质细胞(hUMSCs)培养过程中迁移基因( 、 、 、 和 )以及分化标志物的表达。因此,在处理后的hUMSCs中观察到无精子症样缺失(DAZL)、piwi样RNA介导的基因沉默2(PIWIL2)转录本以及蛋白质的高表达水平。得出的结论是,联合治疗(即MPLA/RA)比单独的每种治疗都有更显著的结果,尽管MPLA和RA可分别被视为迁移和分化的诱导剂。最终,建议将联合治疗作为一种更有效的策略引入,以改善再生医学中的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bd2/7936076/479b1459a539/ijmcm-9-288-g001.jpg

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