College of Biological Science and Medical Engineering, Donghua University, Shanghai, People's Republic of China.
Department of Geriatrics, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
Biomed Mater. 2023 Jun 28;18(4). doi: 10.1088/1748-605X/ace019.
Stem cell therapy has a broad future in treating sensorineural hearing loss in mammals. But how to produce sufficient functional auditory cells including hair cells, supporting cells as well as spiral ganglion neurons from potential stem cells is the bottleneck. In this study, we aimed to simulate inner ear development microenvironment to induce inner ear stem cells to differentiate into auditory cells. The different mass ratios of poly-l-lactic acid/gelatin (PLLA/Gel) scaffolds were fabricated by electrospinning technology to mimic the structure of the native cochlear sensory epithelium. The chicken utricle stromal cells were isolated and cultured, and then seeded on the PLLA/Gel scaffolds. The chicken utricle stromal cell-derived decellularized extracellular matrix (U-dECM)-coated PLLA/Gel bioactive nanofiber scaffolds (U-dECM/PLLA/Gel) were prepared by decellularization. The U-dECM/PLLA/Gel scaffolds were used for culture of inner ear stem cells, and the effects of the modified scaffolds on the differentiation of inner ear stem cells were analyzed by RT-PCR and immunofluorescent staining. The results showed that U-dECM/PLLA/Gel scaffolds possessed good biomechanical properties can significantly promote the differentiation of inner ear stem cells and make them differentiate into auditory cells. Collectively, these findings indicated that U-dECM-coated biomimetic nanomaterials may be a promising strategy for auditory cell production.
干细胞疗法在治疗哺乳动物的感觉神经性听力损失方面具有广阔的前景。但是，如何从潜在的干细胞中产生足够数量的功能性听觉细胞，包括毛细胞、支持细胞和螺旋神经节神经元，是一个瓶颈。在这项研究中，我们旨在模拟内耳发育的微环境，诱导内耳干细胞分化为听觉细胞。通过静电纺丝技术制备不同质量比的聚 L-乳酸/明胶（PLLA/Gel）支架，以模拟天然耳蜗感觉上皮的结构。分离并培养鸡耳石基质细胞，然后将其接种到 PLLA/Gel 支架上。通过去细胞化制备鸡耳石基质细胞衍生的去细胞外基质（U-dECM）涂覆 PLLA/Gel 生物活性纳米纤维支架（U-dECM/PLLA/Gel）。将 U-dECM/PLLA/Gel 支架用于内耳干细胞的培养，并通过 RT-PCR 和免疫荧光染色分析改性支架对内耳干细胞分化的影响。结果表明，U-dECM/PLLA/Gel 支架具有良好的生物力学性能，可以显著促进内耳干细胞的分化，并使其分化为听觉细胞。总之，这些发现表明 U-dECM 涂层仿生纳米材料可能是产生听觉细胞的一种有前途的策略。
