Acid stimulation-induced semi-pluripotent characteristics in human somatic cells

Abstract

Background: Clinical trials of cell-based therapies using induced pluripotent stem (iPS) cells have already been started for several neurological diseases.

Objective: The purpose of the present study was to explore the characteristics and differentiation of somatic cells in vitro undergoing a low pH treatment, so as to provide new therapeutic strategies for treating sensorineural hearing loss.

Methods: Somatic cells were treated with low pH solution to alter their characteristics. In addition, a mouse model of the cochlear lesion was constructed using bilirubin. Subsequently, the characteristics and therapeutic effect of somatic cells undergoing low pH treatment were examined by morphology, alkaline phosphatase (AKP) activity, immunofluorescence assay and q-PCR.

Results: The cells in the experimental group grew better than those in the control group. The AKP activity in the experimental group was higher than that in the control group. The expression of Nanog and Oct4 was both positive in the two groups. When the cells were changed to neurobasal medium, the marker of nestin was positive.

Conclusion: The human somatic cells undergoing a low pH treatment showed the similar characteristics as those of iPS cells, although the functions and therapeutic effect of these altered human somatic cells need to be further studied.

Chinese abstract

背景：使用诱导多能干（IPS）细胞的细胞疗法来治疗若干种神经疾病的临床试验已经开始了。

目的：探讨经体外低pH处理的体细胞的特点和变化, 为治疗感音神经性耳聋提供新的治疗方法。

方法：采用低pH溶液处理体细胞, 改变其特性。此外, 用胆红素建立小鼠耳蜗损伤模型。随后, 通过形态学、AKP活性、免疫荧光分析和q-PCR来检测经低pH处理的体细胞的特征和治疗效果。

结果：实验组细胞生长情况优于对照组。实验组的AKP活性高于对照组。两组患者Nanog和Oct4的表达均为阳性。当细胞转化为神经基底细胞培养基时, 巢蛋白标记物呈阳性。

结论：经低pH处理的人体细胞具有与IPS细胞相似的特性, 但这些经过改变的体细胞的功能和治疗效果有待进一步研究。

Keywords:

• Low pH
• morphology
• AKP activity
• q-PCR
• immunofluorescence assay

Acknowledgements

We thank members of the central laboratory of the General Hospital of Chinese People’s Liberation Army, the Biotechnology Museum of Tsinghua University and Bang Fei Biotech Company of Beijing for their advice and support.

Disclosure statement

There is no conflict of interest among the authors. All of the authors are responsible for the truthfulness of the content and writing of this paper.