Graphene Substrates Promote the Differentiation of Inner Ear Lgr5+ Progenitor Cells Into Hair Cells

Xiaoqiong Ding; Yangnan Hu; Hong Cheng; Xiaoli Zhang; Ling Lu; Song Gao; Cheng Cheng; Lifen Wang; Xiaoyun Qian; Chen Zhang; Renjie Chai; Xia Gao; Zhichun Huang

doi:10.3389/fbioe.2022.927248

Graphene Substrates Promote the Differentiation of Inner Ear Lgr5+ Progenitor Cells Into Hair Cells

Front Bioeng Biotechnol. 2022 Jun 22:10:927248. doi: 10.3389/fbioe.2022.927248. eCollection 2022.

Authors

Xiaoqiong Ding^{1

2}, Yangnan Hu³, Hong Cheng³, Xiaoli Zhang⁴, Ling Lu⁴, Song Gao⁴, Cheng Cheng⁴, Lifen Wang², Xiaoyun Qian⁴, Chen Zhang⁵, Renjie Chai^{2

3

4

5

6

7

8}, Xia Gao¹, Zhichun Huang²

Affiliations

¹ Department of Otorhinolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital, Drum Tower Clinical College of Nanjing Medical University, Nanjing, China.
² Department of Otorhinolaryngology-Head and Neck Surgery, Zhongda Hospital, Southeast University, Nanjing, China.
³ State Key Laboratory of Bioelectronics, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, School of Life Sciences and Technology, Advanced Institute for Life and Health, Southeast University, Nanjing, China.
⁴ Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
⁵ Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, China.
⁶ Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
⁷ Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
⁸ Institute for Stem Cell and Regeneration, Chinese Academy of Science, Beijing, China.

Abstract

The ideal treatment for sensory hearing loss is to regenerate inner ear hair cells (HCs) through stem cell therapy, thereby restoring the function and structure of the cochlea. Previous studies have found that Lgr5+ supporting cells (SCs) in the inner ear can regenerate HCs, thus being considered inner ear progenitor cells. In addition to traditional biochemical factors, physical factors such as electrical conductivity also play a crucial role in the regulation of stem cell proliferation and differentiation. In this study, the graphene substrates were used to culture Lgr5+ progenitor cells and investigated their regulatory effects on cells. It was demonstrated that the graphene substrates displayed great cytocompatibility for Lgr5+ progenitors and promoted their sphere-forming ability. Moreover, more Myosin7a+ cells were found on the graphene substrates compared with tissue culture polystyrene (TCPS). These results suggest that graphene is an efficient interface that can promote the differentiation of Lgr5+ progenitors into HCs, which is great significance for its future application in combination with Lgr5+ cells to regenerate HCs in the inner ear.

Keywords: differentiation; graphene; hair cell regeneration; proliferation; sensorineural hearing loss.