Department of Surgery, Yale School of Medicine, USA; Department of Ophthalmology and Visual Sciences, Yale School of Medicine, USA.
Aier School of Ophthalmology, Central South University, Changsha, China.
Biomaterials. 2018 Feb;154:158-168. doi: 10.1016/j.biomaterials.2017.10.052. Epub 2017 Oct 31.
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.
视网膜变性是发达国家致盲的主要原因。干细胞可以分化为视网膜类器官，用于研究视网膜变性的机制、开发治疗药物，并可能作为替代组织。这些类视网膜的球形性质限制了它们的应用，因为研究人员无法方便地接触到新组织的两面。为了进行组织替代，球形类视网膜无法同时与宿主视网膜色素上皮和剩余的神经感觉视网膜相互作用。为了尝试制作平面类视网膜，我们开发了一种可生物降解的支架，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和免疫印迹确认向视网膜细胞的分化。与其他前脑细胞相比，支架更有利于分化为视网膜细胞类型，但视网膜分层仍很原始。将支架植入视网膜变性的小鼠模型的视网膜下腔时，仅引起轻微的免疫反应。植入物至少存活了 12 周，但有证据表明是细胞质转移而不是植入外核层（感光细胞层）。然而，一些植入的细胞迁移到视网膜的内层，并建立了复杂的神经突树突。
