在有或没有 RPE 损伤的灵长类动物眼中移植 hiPSC-RPE 条带后,进行移植物细胞的扩增。
Graft cell expansion from hiPSC-RPE strip after transplantation in primate eyes with or without RPE damage.
机构信息
Kobe City Eye Hospital, 2-1-8, Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
Department of Ophthalmology, Institute of Biomedical Sciences, Graduate School, Tokushima University, Tokushima, Japan.
出版信息
Sci Rep. 2024 May 2;14(1):10044. doi: 10.1038/s41598-024-60895-w.
Clinical studies using suspensions or sheets of human pluripotent cell-derived retinal pigment epithelial cells (hiPSC-RPE) have been conducted globally for diseases such as age-related macular degeneration. Despite being minimally invasive, cell suspension transplantation faces challenges in targeted cell delivery and frequent cell leakage. Conversely, although the RPE sheet ensures targeted delivery with correct cell polarity, it requires invasive surgery, and graft preparation is time-consuming. We previously reported hiPSC-RPE strips as a form of quick cell aggregate that allows for reliable cell delivery to the target area with minimal invasiveness. In this study, we used a microsecond pulse laser to create a local RPE ablation model in cynomolgus monkey eyes. The hiPSC-RPE strips were transplanted into the RPE-ablated and intact sites. The hiPSC-RPE strip stably survived in all transplanted monkey eyes. The expansion area of the RPE from the engrafted strip was larger at the RPE injury site than at the intact site with no tumorigenic growth. Histological observation showed a monolayer expansion of the transplanted RPE cells with the expression of MERTK apically and collagen type 4 basally. The hiPSC-RPE strip is considered a beneficial transplantation option for RPE cell therapy.
临床研究已经在全球范围内使用人类多能干细胞来源的视网膜色素上皮细胞(hiPSC-RPE)的悬浮液或薄片来治疗年龄相关性黄斑变性等疾病。尽管细胞悬浮液移植是微创的,但在靶向细胞递送和频繁的细胞泄漏方面仍面临挑战。相反,虽然 RPE 薄片能够确保靶向递送和正确的细胞极性,但需要进行侵入性手术,并且移植物制备耗时较长。我们之前曾报道过 hiPSC-RPE 条带作为一种快速细胞聚集体的形式,可实现最小侵入性的可靠细胞递送到目标区域。在这项研究中,我们使用微秒脉冲激光在食蟹猴眼中创建了一个局部 RPE 消融模型。将 hiPSC-RPE 条带移植到 RPE 消融和完整部位。所有移植的猴眼均稳定地存活了 hiPSC-RPE 条带。与完整部位相比,在 RPE 损伤部位,来自移植条带的 RPE 扩展面积更大,没有肿瘤生长。组织学观察显示,移植的 RPE 细胞呈单层扩展,顶端表达 MERTK,基底表达 IV 型胶原。hiPSC-RPE 条带被认为是 RPE 细胞治疗的一种有益的移植选择。