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源自精神分裂症患者皮肤成纤维细胞的人诱导多能干细胞的生成

Generation of Human-induced Pluripotent Stem Cells Derived From Dermal Fibroblast of Schizophrenic Patients.

作者信息

Parvishan Asghar, Joghataei Mohammad Taghi, Kiani Jafar, Shahbazi Ali, Faghihi Faezeh, Ghadiri Mohammad

机构信息

Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.

Student Research Committee, Iran University of Medical Sciences, Tehran, Iran.

出版信息

Basic Clin Neurosci. 2024 May-Jun;15(3):333-342. doi: 10.32598/bcn.2022.3697.1. Epub 2024 May 1.

Abstract

INTRODUCTION

Schizophrenia (SCZ) is a psychiatric disorder caused by environmental, social, and genetic factors. This phenomenon is a severe neuropsychiatric disorder with a 1% worldwide prevalence. As SCZ is an exclusively human disorder, animal models cannot mimic SCZ pathophysiology. Thus, it is crucial to develop a novel human-based specific model of SCZ to elucidate mechanisms of the occurrence of the disease. In this regard, the aim of this study was reprogramming somatic cells to human-induced pluripotent stem cells (hiPSCs), with possible potency to transformed to specific neural stem cells.

METHODS

In the present study, we directly reprogrammed the isolated human ear dermal fibroblasts (HDFs) from schizophrenic patients into hiPSCs using some episomal agents in Matrigel-coated plates. The existence of pluripotency markers was confirmed by the immunocytochemistry (ICC) test and alkaline phosphatase protocol. We performed karyotype analysis to ensure the maintenance of the normal chromosomes.

RESULTS

Analysis of colonies exhibited intense alkaline phosphatase engagement and Oct4, SSEA4, Nanog, and Tra-1-60. HiPSCs showed normal karyotypes and were potent to differentiate into ectoderm, endoderm, and mesoderm.

CONCLUSION

This study showed human dermal mesenchymal fibroblasts taken from schizophrenic patients can be reprogrammed to hiPSCs, with potential to transformation to three germ layers with sufficient expression of relate molecular markers. This is the first steps to produce SCZ specific neural stem cells, which can be used in the assessment of cellular changes in schizophrenia and possible effects of antipsychotic agents. .

摘要

引言

精神分裂症(SCZ)是一种由环境、社会和遗传因素引起的精神障碍。这种现象是一种严重的神经精神疾病,在全球的患病率为1%。由于SCZ是一种仅在人类中出现的疾病,动物模型无法模拟SCZ的病理生理学。因此,开发一种基于人类的新型SCZ特异性模型以阐明该疾病的发病机制至关重要。在这方面,本研究的目的是将体细胞重编程为人类诱导多能干细胞(hiPSC),其有可能转化为特定的神经干细胞。

方法

在本研究中,我们使用一些游离型载体在基质胶包被的培养板中将从精神分裂症患者分离出的人耳皮肤成纤维细胞(HDF)直接重编程为hiPSC。通过免疫细胞化学(ICC)检测和碱性磷酸酶检测证实了多能性标志物的存在。我们进行了核型分析以确保正常染色体的维持。

结果

集落分析显示碱性磷酸酶活性强烈,且存在Oct4、SSEA4、Nanog和Tra-1-60。hiPSC显示出正常的核型,并且有分化为外胚层、内胚层和中胚层的潜力。

结论

本研究表明,取自精神分裂症患者的人皮肤间充质成纤维细胞可以重编程为hiPSC,有转化为三个胚层的潜力,且相关分子标志物表达充分。这是产生SCZ特异性神经干细胞的第一步,可用于评估精神分裂症中的细胞变化以及抗精神病药物的可能作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8606/11470888/3e23cae5572f/BCN-15-333-g001.jpg

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