標題: Laminin modification subretinal bio-scaffold remodels retinal pigment epithelium-driven microenvironment in vitro and in vivo
作者: Peng, Chi-Hsien
Chuang, Jen-Hua
Wang, Mong-Lien
Jhan, Yong-Yu
Chien, Ke-Hung
Chung, Yu-Chien
Hung, Kuo-Hsuan
Chang, Chia-Ching
Lee, Chao-Kuei
Tseng, Wei-Lien
Hwang, De-Kuang
Hsu, Chia-Hsien
Lin, Tai-Chi
Chiou, Shih-Hwa
Chen, Shih-Jen
生物科技學系
Department of Biological Science and Technology
關鍵字: age-related macular degeneration;biomimetic scaffold;pluripotent stem cells;pigment epithelium cells;pigment epithelium-derived factor;Pathology Section
公開日期: 4-Oct-2016
摘要: Advanced age-related macular degeneration (AMD) may lead to geographic atrophy or fibrovascular scar at macular, dysfunctional retinal microenvironment, and cause profound visual loss. Recent clinical trials have implied the potential application of pluripotent cell-differentiated retinal pigment epithelial cells (dRPEs) and membranous scaffolds implantation in repairing the degenerated retina in AMD. However, the efficacy of implanted membrane in immobilization and supporting the viability and functions of dRPEs, as well as maintaining the retinal microenvironment is still unclear. Herein we generated a biomimetic scaffold mimicking subretinal Bruch\'s basement from plasma modified polydimethylsiloxane (PDMS) sheet with laminin coating (PDMS-PmL), and investigated its potential functions to provide a subretinal environment for dRPE-monolayer grown on it. Firstly, compared to non-modified PDMS, PDMS-PmL enhanced the attachment, proliferation, polarization, and maturation of dRPEs. Second, PDMS-PmL increased the polarized tight junction, PEDF secretion, melanosome pigment deposit, and phagocytotic-ability of dRPEs. Third, PDMS-PmL was able to carry a dRPEs/ photoreceptor-precursors multilayer retina tissue. Finally, the in vivo subretinal implantation of PDMS-PmL in porcine eyes showed well-biocompatibility up to 2-year follow-up. Notably, multifocal ERGs at 2-year follow-up revealed well preservation of macular function in PDMS-PmL, but not PDMS, transplanted porcine eyes. Trophic PEDF secretion of macular retina in PDMS-PmL group was also maintained to preserve retinal microenvironment in PDMS-PmL eyes at 2 year. Taken together, these data indicated that PDMS-PmL is able to sustain the physiological morphology and functions of polarized RPE monolayer, suggesting its potential of rescuing macular degeneration in vivo.
URI: http://dx.doi.org/10.18632/oncotarget.11502
http://hdl.handle.net/11536/132883
ISSN: 1949-2553
DOI: 10.18632/oncotarget.11502
期刊: ONCOTARGET
Volume: 7
Issue: 40
起始頁: 64631
結束頁: 64648
Appears in Collections:Articles