Decellularised extracellular matrix-derived peptides from neural retina and retinal pigment epithelium enhance the expression of synaptic markers and light responsiveness of human pluripotent stem cell derived retinal organoids
Decellularised extracellular matrix-derived peptides from neural retina and retinal pigment epithelium enhance the expression of synaptic markers and light responsiveness of human pluripotent stem cell derived retinal organoids
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DOI：
10.1016/j.biomaterials.2019.01.028
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发表时间：
2019-04-01
期刊：
影响因子：
14
通讯作者：
Lako, Majlinda
中科院分区：
文献类型：
--
作者：
Dorgau, Birthe;Felemban, Majed;Lako, Majlinda
组织特异性细胞外基质（ECM）提供结构支持，并能够获得分子信号和代谢产物，这对于指导干细胞更新和分化至关重要。为了在体外模拟这种现象，已经开发了组织去细胞化方法，从而产生了具有与天然组织相当的物理和生物化学性质的天然ECM支架，并且由于易于标准化生产和恒定可用性，目前在组织工程和再生疗法中获得了牵引力。在这篇手稿中，我们报告了从神经视网膜（decel NR）和视网膜色素上皮（decel RPE）成功产生脱细胞ECM衍生肽，以及它们对人多能干细胞（hPSC）分化为视网膜类器官的影响。我们表明，培养基补充decel RPE和RPE条件培养基（CM RPE）显着增加视杆细胞的产生，而decel NR和decel RPE的添加显着增强带状突触标志物的表达和视网膜类器官的光响应。光感受器成熟、视网膜细胞之间正确突触的形成以及来自hPSC衍生的视网膜类器官的稳健光响应的记录仍然是再生医学领域尚未解决的挑战。如本文所示，响应于添加来自RPE和神经视网膜的去细胞化基质而增强的视杆光感受器分化、突触发生和光响应在用于药物筛选、组织工程和再生医学的视网膜类器官的产生方面提供了新的和实质性的进展。
Tissue specific extracellular matrices (ECM) provide structural support and enable access to molecular signals and metabolites, which are essential for directing stem cell renewal and differentiation. To mimic this phenomenon in vitro, tissue decellularisation approaches have been developed, resulting in the generation of natural ECM scaffolds that have comparable physical and biochemical properties of the natural tissues and are currently gaining traction in tissue engineering and regenerative therapies due to the ease of standardised production, and constant availability. In this manuscript we report the successful generation of decellularised ECM-derived peptides from neural retina (decel NR) and retinal pigment epithelium (decel RPE), and their impact on differentiation of human pluripotent stem cells (hPSCs) to retinal organoids. We show that culture media supplementation with decel RPE and RPE-conditioned media (CM RPE) significantly increases the generation of rod photoreceptors, whilst addition of decel NR and decel RPE significantly enhances ribbon synapse marker expression and the light responsiveness of retinal organoids. Photoreceptor maturation, formation of correct synapses between retinal cells and recording of robust light responses from hPSC-derived retinal organoids remain unresolved challenges for the field of regenerative medicine. Enhanced rod photoreceptor differentiation, synaptogenesis and light response in response to addition of decellularised matrices from RPE and neural retina as shown herein provide a novel and substantial advance in generation of retinal organoids for drug screening, tissue engineering and regenerative medicine.