Salas Anna, Duarri Anna, Fontrodona Laura, Ramírez Diana Mora, Badia Anna, Isla-Magrané Helena, Ferreira-de-Souza Barbara, Zapata Miguel Ángel, Raya Ángel, Veiga Anna, García-Arumí José
Ophthalmology Research Group, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, 08035 Barcelona, Spain.
Barcelona Stem Cell Bank, Regenerative Medicine Program, IDIBELL, 08908 Hospitalet de Llobregat, Spain.
Mol Ther Methods Clin Dev. 2021 Feb 10;20:688-702. doi: 10.1016/j.omtm.2021.02.006. eCollection 2021 Mar 12.
Photoreceptor loss is the principal cause of blindness in retinal degenerative diseases (RDDs). Whereas some therapies exist for early stages of RDDs, no effective treatment is currently available for later stages, and once photoreceptors are lost, the only option to rescue vision is cell transplantation. With the use of the Royal College of Surgeons (RCS) rat model of retinal degeneration, we sought to determine whether combined transplantation of human-induced pluripotent stem cell (hiPSC)-derived retinal precursor cells (RPCs) and retinal pigment epithelial (RPE) cells was superior to RPE or RPC transplantation alone in preserving retinal from degeneration. hiPSC-derived RPCs and RPE cells expressing (GFP) were transplanted into the subretinal space of rats. monitoring showed that grafted cells survived 12 weeks in the subretinal space, and rats treated with RPE + RPC therapy exhibited better conservation of the outer nuclear layer (ONL) and visual response than RPE-treated or RPC-treated rats. Transplanted RPE cells integrated in the host RPE layer, whereas RPC mostly remained in the subretinal space, although a limited number of cells integrated in the ONL. In conclusion, the combined transplantation of hiPSC-derived RPE and RPCs is a potentially superior therapeutic approach to protect retina from degeneration in RDDs.
光感受器丧失是视网膜退行性疾病（RDD）致盲的主要原因。虽然针对RDD的早期阶段存在一些治疗方法，但目前对于晚期阶段尚无有效的治疗方法，而且一旦光感受器丧失，挽救视力的唯一选择就是细胞移植。利用皇家外科医学院（RCS）大鼠视网膜变性模型，我们试图确定人诱导多能干细胞（hiPSC）来源的视网膜前体细胞（RPC）和视网膜色素上皮（RPE）细胞联合移植在保护视网膜免于变性方面是否优于单独的RPE或RPC移植。将表达绿色荧光蛋白（GFP）的hiPSC来源的RPC和RPE细胞移植到大鼠的视网膜下间隙。监测显示移植的细胞在视网膜下间隙存活了12周，接受RPE + RPC治疗的大鼠在外核层（ONL）和视觉反应方面比接受RPE治疗或RPC治疗的大鼠表现出更好的保存情况。移植的RPE细胞整合到宿主RPE层中，而RPC大多留在视网膜下间隙，尽管有少数细胞整合到ONL中。总之，hiPSC来源的RPE和RPC联合移植是一种潜在的更优治疗方法，可保护视网膜在RDD中免于变性。
