Redenti Stephen, Neeley William L, Rompani Santiago, Saigal Sunita, Yang Jing, Klassen Henry, Langer Robert, Young Michael J
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Biomaterials. 2009 Jul;30(20):3405-14. doi: 10.1016/j.biomaterials.2009.02.046. Epub 2009 Apr 9.
Retinal degenerations cause permanent visual loss and affect millions world-wide. Presently, a novel treatment highlights the potential of using biodegradable polymer scaffolds to induce differentiation and deliver retinal progenitor cells for cell replacement therapy. In this study, we engineered and analyzed a micro-fabricated polymer, poly(glycerol sebacate) (PGS) scaffold, whose useful properties include biocompatibility, elasticity, porosity, and a microtopology conducive to mouse retinal progenitor cell (mRPC) differentiation. In vitro proliferation assays revealed that PGS held up to 86,610 (+/-9993) mRPCs per square millimeter, which were retained through simulated transplantations. mRPCs adherent to PGS differentiated toward mature phenotypes as evidenced by changes in mRNA, protein levels, and enhanced sensitivity to glutamate. Transplanted composites demonstrated long-term mRPC survival and migrated cells exhibited mature marker expression in host retina. These results suggest that combining mRPCs with PGS scaffolds for subretinal transplantation is a practical strategy for advancing retinal tissue engineering as a restorative therapy.
视网膜变性会导致永久性视力丧失,影响全球数百万人。目前,一种新型治疗方法凸显了使用可生物降解聚合物支架诱导分化并递送视网膜祖细胞进行细胞替代疗法的潜力。在本研究中,我们设计并分析了一种微加工的聚合物——聚癸二酸甘油酯(PGS)支架,其有用特性包括生物相容性、弹性、孔隙率以及有利于小鼠视网膜祖细胞(mRPC)分化的微观拓扑结构。体外增殖试验表明,PGS每平方毫米可容纳多达86,610(±9993)个mRPC,通过模拟移植可保留这些细胞。附着在PGS上的mRPC向成熟表型分化,这通过mRNA、蛋白质水平的变化以及对谷氨酸敏感性的增强得以证明。移植的复合物显示mRPC长期存活,迁移的细胞在宿主视网膜中表现出成熟标记物表达。这些结果表明,将mRPC与PGS支架结合用于视网膜下移植是推进视网膜组织工程作为一种修复疗法的实用策略。