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诱导多能干细胞来源的角膜内皮样细胞用于细胞治疗。

Corneal Endothelial-like Cells Derived from Induced Pluripotent Stem Cells for Cell Therapy.

机构信息

Tissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore 169856, Singapore.

Ophthalmology and Visual Sciences Academic Clinical Program, SingHealth and Duke-NUS Medical School, Singapore 169857, Singapore.

出版信息

Int J Mol Sci. 2023 Aug 4;24(15):12433. doi: 10.3390/ijms241512433.

Abstract

Corneal endothelial dysfunction is one of the leading causes of corneal blindness, and the current conventional treatment option is corneal transplantation using a cadaveric donor cornea. However, there is a global shortage of suitable donor graft material, necessitating the exploration of novel therapeutic approaches. A stem cell-based regenerative medicine approach using induced pluripotent stem cells (iPSCs) offers a promising solution, as they possess self-renewal capabilities, can be derived from adult somatic cells, and can be differentiated into all cell types including corneal endothelial cells (CECs). This review discusses the progress and challenges in developing protocols to induce iPSCs into CECs, focusing on the different media formulations used to differentiate iPSCs to neural crest cells (NCCs) and subsequently to CECs, as well as the characterization methods and markers that define iPSC-derived CECs. The hurdles and solutions for the clinical application of iPSC-derived cell therapy are also addressed, including the establishment of protocols that adhere to good manufacturing practice (GMP) guidelines. The potential risks of genetic mutations in iPSC-derived CECs associated with long-term in vitro culture and the danger of potential tumorigenicity following transplantation are evaluated. In all, this review provides insights into the advancement and obstacles of using iPSC in the treatment of corneal endothelial dysfunction.

摘要

角膜内皮功能障碍是导致角膜盲的主要原因之一,目前常规的治疗方法是使用尸体供体角膜进行角膜移植。然而,全球供体移植物材料短缺,因此需要探索新的治疗方法。基于诱导多能干细胞(iPSC)的干细胞再生医学方法提供了一个有前途的解决方案,因为它们具有自我更新能力,可从成体体细胞中获得,并可分化为包括角膜内皮细胞(CEC)在内的所有细胞类型。本综述讨论了开发诱导 iPSC 分化为 CEC 的方案的进展和挑战,重点介绍了用于将 iPSC 分化为神经嵴细胞(NCC)并随后分化为 CEC 的不同培养基配方,以及定义 iPSC 衍生的 CEC 的特征化方法和标记物。还讨论了 iPSC 衍生细胞治疗的临床应用所面临的障碍和解决方案,包括建立符合良好生产规范(GMP)指南的方案。评估了与长期体外培养相关的 iPSC 衍生 CEC 中遗传突变的潜在风险以及移植后潜在致瘤性的危险。总之,本综述深入了解了使用 iPSC 治疗角膜内皮功能障碍的进展和障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a1d/10418878/398911d33e04/ijms-24-12433-g005.jpg

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