人视网膜色素上皮细胞替代疗法治疗视网膜退行性疾病

Human retinal pigment epithelial cell replacement therapy for retinal degenerative diseases

视网膜色素上皮(retinal pigment epithelium,RPE)细胞替代疗法是治疗视网膜退行性病变的潜在方法。在眼部进行RPE细胞替代治疗有独特优势。替代用RPE细胞可源于干细胞和体细胞。前者包括胚胎干细胞(embryonic stem cell,ESC)-RPE及诱导多能干细胞(induced pluripotent stem cell,iPSC)-RPE;后者分为成年人来源(自体或异体)及胎儿来源(Fetal-RPE)。RPE细胞替代治疗的临床研究尚处于早期阶段。目前人ESC-RPE细胞、人iPSC-RPE细胞、人Fetal-RPE细胞治疗视网膜退行性疾病均处于临床前研究及临床研究阶段。临床试验结果显示部分患者视功能改善。但ESC-RPE及Fetal-RPE均无法避免免疫排斥反应,使用免疫抑制剂的并发症亦值得关注,移植细胞能否长期存活尚需进一步观察。iPSC诱导方案、ESC及iPSC分化为RPE细胞的方法也未形成统一、规范的指南,合理的治疗时间窗、细胞植片制作及移植术的改良是保证效果的关键。(国际眼科纵览,2020,44:419-426)

Retinal pigment epithelium(RPE)cell replacement therapy is a potential method for the treatment of retinal degenerative disease.Unique advantages for RPE cell replacement therapy exist in treatment for the eye.Alternative RPE cells can derive from both stem cells and somatic cells.The former includes embryonic stem cell(ESC)-RPE and induced pluripotent stem cell(iPSC)-RPE.The latter is divided into adult origin(autologous or allogeneic)and fetal origin(Fetal-RPE).The clinical research of RPE cell replacement therapy is still in the early stage.At present,human ESC-RPE,human iPSC-RPE,and human Fetal-RPE cell replacement therapy for retinal degenerative diseases are all still in the preclinical and clinical research stages.In clinical trials,the visual function of some patients has improved,but neither ESC-RPE nor Fetal-RPE can avoid immune rejection.The complications of immunosuppressive agents are also worthy of attention.Whether the transplanted cells can survive for a long time needs further observation.The iPSC induction regimen,the method of ESC and iPSC differentiation into RPE cells have not formed a unified and standardized guide.Reasonable treatment time window,improvement of cell graft production and transplantation are the keys to ensure the effect of treatment.(Int Rev Ophthalmol,2020,44:419-426)