背景:干细胞临床试验中通常采用药物免疫抑制方案来减轻宿主免疫排斥并促进移植细胞的存活和活力。免疫抑制和细胞存活已经在视网膜和脊髓组织中被广泛研究。干细胞疗法的适用性正在迅速扩展到其他感觉器官,例如耳朵和听力。由于再生疗法指向新的领域,需要对免疫抑制策略及其功效有更深入的了解,以促进向器官特异性生物微环境的转化.
目的:本系统综述评价了目前关于视网膜和神经细胞干细胞试验中使用的免疫抑制策略的文献。
方法:本系统评价按照系统评价和荟萃分析指南的首选报告项目进行。纳入标准包括提供神经或视网膜细胞数据的研究,作为人体临床试验的一部分,详细说明了所用的免疫抑制方案。排除标准包括非英语语言研究,动物研究,评论文章,病例报告,社论,和信件。Medline数据库,Embase,Scopus,WebofScience,从成立到2024年2月,搜索了Cochrane图书馆。使用ROBINS-I工具评估偏倚风险。
结果:18篇文章符合纳入标准。九篇文章涉及视网膜细胞,5有关脊髓损伤,和4有关肌萎缩侧索硬化症。在确定的研究中通常采用多药和短期免疫抑制方案。在接受治疗的患者中检测到的免疫反应很少见。常见的免疫抑制模式包括他克莫司,霉酚酸酯和逐渐减少剂量的类固醇。在一些有关视网膜疾病的研究中采用了类固醇的局部免疫抑制。
结论:对于大多数纳入研究,短期的全身性免疫抑制疗法似乎是有效的。其中一些显示移植细胞在免疫抑制停止后数月至数年存活。需要进行更长期的随访,以查看情况是否仍然如此。与免疫抑制相关的副作用并不常见。
BACKGROUND: Pharmacologic immunosuppression regimes are commonly employed in stem cell clinical trials to mitigate host immune rejection and promote survival and viability of transplanted cells. Immunosuppression and cell survival has been extensively studied in retinal and spinal tissues. The applicability of stem cell therapy is rapidly expanding to other sensory organs such as the ear and hearing. As regenerative therapy is directed to new areas, a greater understanding of immunosuppression strategies and their efficacy is required to facilitate translation to organ-specific biologic microenvironments.
OBJECTIVE: This systematic review appraises the current literature regarding immunosuppression strategies employed in stem cell trials of retinal and neural cells.
METHODS: This systematic review was performed in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria included studies presenting data on neural or retinal cells as part of an in-human clinical trial that detailed the immunosuppression regime used. Exclusion criteria included non-English language studies, animal studies, review articles, case reports, editorials, and letters. The databases Medline, Embase, Scopus, Web of Science, and the Cochrane Library were searched from inception to February 2024. Risk of bias was evaluated using the ROBINS-I tool.
RESULTS: Eighteen articles fit the inclusion criteria. Nine articles concerned retinal cells, 5 concerned spinal cord injury, and 4 concerned amyotrophic lateral sclerosis. A multi-drug and short-term immunosuppression regime were commonly employed in the identified studies. Detected immune responses in treated patients were rare. Common immunosuppression paradigms included tacrolimus, mycophenolate mofetil and tapering doses of steroids. Local immunosuppression with steroids was employed in some studies concerning retinal diseases.
CONCLUSIONS: A short-term course of systemic immunosuppression seemed efficacious for most included studies, with some showing grafted cells viable months to years after immunosuppression had stopped. Longer-term follow-up is required to see if this remains the case. Side effects related to immunosuppression were uncommon.