網膜オルガノイドを用いた糖尿病網膜症モデルの開発

抄録

Stem cell-derived retinal organoids (ROs) have been investigated for applications in regenerative medicine, retinal disease models, and the safety evaluation of compounds. Although the advent of 3D organoids has provided innovative avenues, some unresolved limitations are present in organoid research: passive diffusion of oxygen and nutrients limits organoid growth and functional gain. Vascularization might overcome the aforementioned problems because oxygen and nutrient enter into the organoid core. In this study, ROs and vascular organoids (VOs) were generated from healthy human iPS cells. By co-culturing them, we attempted to create vascular-like structures in ROs. Co-culture of ROs and vascular organoids showed type IV collagen and CD31 positive vascular-like structures in retinal organoids. When Co-culture of retinal organoids and vascular organoids were cultured under hyperglycaemic conditions, the basement membrane was thickening in VOs, occludin expression was significantly decreased, and the size of ROs themselves decreased. In conclusion, the co-culture of ROs with VOs made it possible to produce ROs with vascular-like structures, and vascularized ROs could respond to the severe diabetic retinopathy model.