Faura Georgina, Studenovska Hana, Sekac David, Ellederova Zdenka, Petrovski Goran, Eide Lars
Department of Medical Biochemistry, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0372 Oslo, Norway.
CIDETEC, Basque Research and Technology Alliance (BRTA), 20014 Donostia-San Sebastián, Spain.
Biomedicines. 2024 Apr 26;12(5):966. doi: 10.3390/biomedicines12050966.
Age-related macular degeneration (AMD) is the most frequent cause of blindness in developed countries. The replacement of dysfunctional human retinal pigment epithelium (hRPE) cells by the transplantation of in vitro-cultivated hRPE cells to the affected area emerges as a feasible strategy for regenerative therapy. Synthetic biomimetic membranes arise as powerful hRPE cell carriers, but as biodegradability is a requirement, it also poses a challenge due to its limited durability. hRPE cells exhibit several characteristics that putatively respond to the type of membrane carrier, and they can be used as biomarkers to evaluate and further optimize such membranes. Here, we analyze the pigmentation, transepithelial resistance, genome integrity, and maturation markers of hRPE cells plated on commercial polycarbonate (PC) versus in-house electrospun polylactide-based (PLA) membranes, both enabling separate apical/basolateral compartments. Our results show that PLA is superior to PC-based membranes for the cultivation of hRPEs, and the BEST1/RPE65 maturation markers emerge as the best biomarkers for addressing the quality of hRPE cultivated in vitro. The stability of the cultures was observed to be affected by PLA aging, which is an effect that could be partially palliated by the coating of the PLA membranes.
年龄相关性黄斑变性（AMD）是发达国家中导致失明的最常见原因。通过将体外培养的人视网膜色素上皮（hRPE）细胞移植到病变区域来替代功能失调的hRPE细胞，已成为一种可行的再生治疗策略。合成仿生膜作为强大的hRPE细胞载体出现，但由于需要生物可降解性，其有限的耐久性也带来了挑战。hRPE细胞表现出一些可能对膜载体类型有反应的特征，它们可以用作生物标志物来评估和进一步优化此类膜。在这里，我们分析了接种在商业聚碳酸酯（PC）膜与自制电纺聚丙交酯基（PLA）膜上的hRPE细胞的色素沉着、跨上皮电阻、基因组完整性和成熟标志物，这两种膜都能形成独立的顶侧/基底外侧区室。我们的结果表明，PLA膜在培养hRPE细胞方面优于PC基膜，并且BEST1/RPE65成熟标志物是评估体外培养的hRPE细胞质量的最佳生物标志物。观察到培养物的稳定性受PLA老化的影响，而PLA膜涂层可部分缓解这种影响。
