关键词: Atoh1 Bone marrow mesenchymal stem cells Hair cell regeneration Neural stem cells

来  源:   DOI:10.1016/j.heliyon.2024.e32952   PDF(Pubmed)

Abstract:
Sensorineural hearing loss (SNHL) is a prevalent condition in otolaryngology. A key obstacle is finding effective strategies for regenerating damaged cochlear hair cells in adult animals. A practical and reliable approach has been developed to create a superior cell source for stem cell transplantation in the inner ear to treat SNHL. Atoh1 is involved in the differentiation of neurons, intestinal secretory cells, and mechanoreceptors including auditory hair cells, and thus plays an important role in neurogenesis. Lentivirus-mediated transfection of bone marrow mesenchymal stem cells (BMSCs) was utilized to achieve stable expression of the essential transcription factor Atoh1, which is crucial for developing auditory hair cells without compromising cell survival. By manipulating the induction conditions through altering the cell growth environment using anti-adherent culture, the synergistic impact of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) was effectively applied to significantly improve the differentiation efficiency of bone marrow-derived mesenchymal stem cells (BMSC) into neural stem cells (NSCs) following Atoh1 transfection, thereby reducing the induction time. The study indicated that the newly proposed transdifferentiation method effectively transformed BMSCs into NSCs in a controlled environment, presenting a potential approach for stem cell transplantation to promote hair cell regeneration.
摘要:
感觉神经性听力损失(SNHL)是耳鼻喉科的常见病。一个关键的障碍是找到再生成年动物受损耳蜗毛细胞的有效策略。已开发出一种实用可靠的方法,为内耳干细胞移植治疗SNHL创造了优越的细胞源。Atoh1参与神经元的分化,肠道分泌细胞,和包括听觉毛细胞在内的机械感受器,因此在神经发生中起着重要作用。慢病毒介导的骨髓间充质干细胞(BMSCs)的转染被用来实现必需转录因子Atoh1的稳定表达,这对于发育听觉毛细胞而不损害细胞存活至关重要。通过使用抗贴壁培养改变细胞生长环境来操纵诱导条件,碱性成纤维细胞生长因子(bFGF)和表皮生长因子(EGF)的协同作用可显著提高Atoh1转染后骨髓间充质干细胞(BMSC)向神经干细胞(NSC)的分化效率,从而减少诱导时间。研究表明,新提出的转分化方法在受控环境中有效地将BMSCs转化为NSCs,提供干细胞移植促进毛细胞再生的潜在途径。
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