The world’s first clinical trial using iPS cell sheets for corneal epithelial stem cell deficiency
The world’s first clinical trial using iPS cell sheets for corneal epithelial stem cell deficiency
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全球首个使用 iPS 细胞片治疗角膜上皮干细胞缺陷的临床试验
DOI：
10.15761/nfo.1000234
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Nancy S. Jecker
中科院分区：
文献类型：
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作者：
A. Akabayashi;E. Nakazawa;Nancy S. Jecker
背景：世界上第一个使用诱导多能干细胞片治疗角膜上皮干细胞缺乏症的临床试验正在进行中。在其他地方，我们分析了该协议，并认为它基本上是道德的。辩论要点：我们提出三个伦理问题。首先，与其他治疗方法相比，新疗法应表现出更大的治疗效果。其次，成本是广泛采用的潜在障碍。第三，由于日本依赖其他国家的捐赠者，日本的眼部捐赠者短缺引发了对公平性的伦理担忧结论：虽然这种新的眼部治疗有许多问题需要讨论和解决，但我们相信眼科领域将在追求iPSC临床研究中承担道德领导作用。背景2018年12月26日，日本大坂大学审查委员会有条件地批准了一项临床试验，用于角膜上皮干细胞缺乏症患者移植来自诱导多能干细胞（iPSC）的角膜细胞片[1]。我们之前在一项针对心力衰竭患者的单独iPSC移植研究中反对该方案，认为这在伦理上是不允许的[2]。然而，最新角膜试验的方案似乎非常符合伦理标准。它在处理不良事件（排斥反应或致瘤性）方面似乎完全可靠，因为移植的角膜片可以很容易地取出。由于新的研究已经在进行中，伦理讨论更加重要。辩论要点下面，我们提出了三点辩论这个新兴的治疗。首先，这项研究的潜在益处似乎证明了研究对象所面临的风险。iPSC片状移植物在质量和治疗效果上是否真的能超过同种异体捐赠的眼移植物或羊膜，这一问题需要严格的科学评估。本移植研究的受试者为角膜上皮干细胞缺乏症患者。一些眼科专家指出，在其他角膜疾病中，内皮功能障碍特别突出。iPSC片层主要替代上皮。另一方面，羊膜在某些参数内显示出有效性的记录。证明更大的治疗效果将是增加角膜移植方法的另一种未来选择的关键。* 通信地址：Akira Akabayashi，日本东京大学医学研究生院公共卫生学院生物医学伦理学系，电子邮件：akirasan-tky@umin.ac.jp
Background: The world’s first clinical trial using induced pluripotent stem cell sheets for corneal epithelial stem cell deficiency is underway. Elsewhere, we have analysed the protocol and argued it basically ethical. Main points for debates: We raise three ethical points. First, the new therapy should demonstrate greater therapeutic effects when compared with other treatment methods. Second, cost is a potential barrier to widespread adoption. Third, the shortage of eye donors in Japan raises ethical concerns of fairness, as Japan relies on donors in other countries Conclusion: While there are many issues to be debated and addressed for this new eye therapy, we believe the ophthalmology field will assume moral leadership in the pursuit of iPSC clinical research. Background On December 26, 2018, the review committee of Osaka University, Japan, granted conditional approval for a clinical trial to transplant corneal cell sheets from induced pluripotent stem cells (iPSC) in patients with corneal epithelial stem cell deficiency [1]. We previously objected to the protocol in a separate iPSC transplantation study for heart failure patients as ethically impermissible [2]. However, the protocol in the latest corneal trials appears to meet ethical standards very well. It appears to be fully reliable in its handling of adverse events (rejection or tumorigenicity), as transplanted corneal sheets can be easily removed. Since the new study is already underway, an ethical discussion is even more critical. Main points for debates Below, we raise three points for debate for this up and coming therapy. First, the potential benefits of the study seem to warrant the risk to which research subjects are exposed. The question of whether iPSC sheet grafts can truly surpass allogeneic donated eye transplants or amniotic membranes in quality and therapeutic effects warrants rigorous scientific assessment. The subjects in this transplant study are patients with corneal epithelial stem cell deficiency. Some ophthalmology specialists note that in other cornea diseases, endothelial dysfunction is particularly salient. iPSC sheets replace mainly the epithelium. On the other hand, amniotic membrane demonstrates a record of effectiveness within certain parameters. Demonstrating greater therapeutic effects will be key to adding another future option to cornea transplant methods. *Correspondence to: Akira Akabayashi, Department of Biomedical Ethics, School of Public Health, University of Tokyo Graduate School of Medicine, Tokyo, Japan, E-Mail: akirasan-tky@umin.ac.jp