Centre for Stem Cell Biology & Department of Biomedical Sciences, University of Sheffield, Alfred Denny Building, Western Bank, Sheffield S10 2TN, UK.
Regen Med. 2012 Nov;7(6):757-67. doi: 10.2217/rme.12.58.
Mouse mesenchymal stem cells (MSCs) can generate sensory neurons and produce inner ear hair cell-like cells. An equivalent source from humans is highly desirable, given their potential application in patient-specific regenerative therapies for deafness. In this study, we explored the ability of human MSCs (hMSCs) to differentiate into otic lineages.
MATERIALS & METHODS: hMSCs were exposed to culture media conditioned by human fetal auditory stem cells.
Conditioned media induced the expression of otic progenitor markers PAX8, PAX2, GATA3 and SOX2. After 4 weeks, cells coexpressed ATOH1, MYO7A and POU4F3 (indicators of hair cell lineage) or neuronal markers NEUROG1, POU4F1 and NEFH. Inhibition of WNT signaling prevented differentiation into otic progenitors, while WNT activation partially phenocopied results seen with the conditioned media.
This study demonstrates that hMSCs can be driven to express key genes found in the otic lineages and thereby promotes their status as candidates for regenerative therapies for deafness.
鼠间质干细胞(MSCs)可分化为感觉神经元,并产生内耳毛细胞样细胞。鉴于其在针对耳聋的患者特异性再生疗法中的潜在应用,从人类中获得等效来源是非常理想的。在这项研究中,我们探讨了人 MSCs(hMSCs)分化为耳原基谱系的能力。
将 hMSCs 暴露于经人胎儿听觉干细胞条件化的培养基中。
条件培养基诱导了耳原基祖细胞标志物 PAX8、PAX2、GATA3 和 SOX2 的表达。4 周后,细胞共表达 ATOH1、MYO7A 和 POU4F3(毛细胞谱系的标志物)或神经元标志物 NEUROG1、POU4F1 和 NEFH。WNT 信号通路的抑制阻止了向耳原基细胞的分化,而 WNT 的激活部分模拟了条件培养基的结果。
这项研究表明,hMSCs 可被诱导表达在耳原基谱系中发现的关键基因,从而增强了它们作为耳聋再生疗法候选物的地位。