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A biodegradable scaffold enhances differentiation of embryonic stem cells into a thick sheet of retinal cells
Biomaterials ( IF 14.0 ) Pub Date : 2017-10-31 , DOI: 10.1016/j.biomaterials.2017.10.052
Deepti Singh , Shao-Bin Wang , Tina Xia , Laurel Tainsh , Maryam Ghiassi-Nejad , Tao Xu , Shaomin Peng , Ron A. Adelman , Lawrence J. Rizzolo

Retinal degeneration is a leading cause of blindness in developed countries. Stem cells can be differentiated into retinal organoids to study mechanisms of retinal degeneration, develop therapeutic agents, and potentially serve as replacement tissues. The spherical nature of these retinoids limits their utility, because the investigator lacks ready access to both sides of the neo-tissue. For tissue-replacement, spherical retinoids are unable to interact simultaneously with the host retinal pigment epithelium and remaining neurosensory retina. To attempt making a planar retinoid, we developed a biodegradable scaffold that simulates the extracellular matrix of the neurosensory retina. Human embryonic stem cells were seeded on the scaffold. Differentiation into retinal cells was confirmed by quantitative RT-PCR, confocal immunocytochemistry, and immunoblotting. The scaffold favored differentiation into retinal cell types over other anterior forebrain cells, but retinal lamination was rudimentary. The cultures elicited a minimal immune response when implanted into the subretinal space of a mouse model of retinal degeneration. The implants survived for at least 12 weeks, but there was evidence of cytoplasmic transfer rather than implantation into the outer nuclear layer (photoreceptor layer). However, some implanted cells migrated to the inner layers of the retina and established elaborate arbors of neurites.

中文翻译:

可生物降解的支架增强了胚胎干细胞向厚厚的视网膜细胞薄片分化的能力

视网膜变性是发达国家失明的主要原因。干细胞可以分化为视网膜类器官,以研究视网膜变性的机制,开发治疗剂,并有可能作为替代组织。这些类维生素A的球形性质限制了它们的实用性,因为研究人员无法轻松接近新组织的两侧。对于组织置换,球形类维生素A不能与宿主视网膜色素上皮和其余的神经感觉视网膜同时相互作用。为了尝试制作平面类视黄醇,我们开发了一种可生物降解的支架,该支架可模拟神经感觉视网膜的细胞外基质。将人胚胎干细胞接种在支架上。通过定量RT-PCR,共聚焦免疫细胞化学证实了向视网膜细胞的分化,和免疫印迹。支架比其他前脑细胞更倾向于分化为视网膜细胞类型,但视网膜层压是基本的。当植入视网膜变性小鼠模型的视网膜下间隙时,培养物引起最小的免疫反应。植入物存活了至少12周,但是有证据表明细胞质转移,而不是植入到外核层(感光层)中。然而,一些植入的细胞迁移到视网膜的内层并建立了精细的神经突柄。植入物存活了至少12周,但是有证据表明细胞质转移,而不是植入到外核层(感光层)中。然而,一些植入的细胞迁移到视网膜的内层并建立了精细的神经突柄。植入物存活了至少12周,但是有证据表明细胞质转移,而不是植入到外核层(感光层)中。然而,一些植入的细胞迁移到视网膜的内层并建立了精细的神经突柄。
更新日期:2017-10-31
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