Tissue engineering RPE sheet derived from hiPSC-RPE cell spheroids supplemented with Y-27632 and RepSox

IF 5.7 3区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

Journal of Biological Engineering Pub Date : 2024-01-16 DOI:10.1186/s13036-024-00405-8

Wenxuan Wang, Tingting Yang, Sihui Chen, Liying Liang, Yingxin Wang, Yin Ding, Wei Xiong, Xiuhong Ye, Yonglong Guo, Shuhao Shen, Hang Chen, Jiansu Chen

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引用次数: 0

Abstract

Retinal pigment epithelium (RPE) cell therapy is a promising way to treat many retinal diseases. However, obtaining transplantable RPE cells is time-consuming and less effective. This study aimed to develop novel strategies for generating engineered RPE patches with physiological characteristics. Our findings revealed that RPE cells derived from human induced pluripotent stem cells (hiPSCs) successfully self-assembled into spheroids. The RPE spheroids treated with Y27632 and Repsox had increased expression of epithelial markers and RPE-specific genes, along with improved cell viability and barrier function. Transcriptome analysis indicated enhanced cell adhesion and extracellular matrix (ECM) organization in RPE spheroids. These RPE spheroids could be seeded and bioprinted on collagen vitrigel (CV) membranes to construct engineered RPE sheets. Circular RPE patches, obtained by trephining a specific section of the RPE sheet, exhibited abundant microvilli and pigment particles, as well as reduced proliferative capacity and enhanced maturation. Our study suggests that the supplementation of small molecules and 3D spheroid culture, as well as the bioprinting technique, can be effective methods to promote RPE cultivation and construct engineered RPE sheets, which may support future clinical RPE cell therapy and the development of RPE models for research applications.

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由添加了 Y-27632 和 RepSox 的 hiPSC-RPE 细胞球形成的组织工程 RPE 薄膜

视网膜色素上皮（RPE）细胞疗法是治疗多种视网膜疾病的一种很有前景的方法。然而，获得可移植的 RPE 细胞耗时且效果不佳。本研究旨在开发新的策略，生成具有生理特性的工程RPE补片。我们的研究结果表明，从人类诱导多能干细胞（hiPSCs）中提取的 RPE 细胞成功地自我组装成球体。用Y27632和Repsox处理的RPE球体上皮标志物和RPE特异性基因的表达增加，细胞活力和屏障功能也得到改善。转录组分析表明，RPE球体内的细胞粘附性和细胞外基质（ECM）组织得到了增强。这些 RPE 球形体可在胶原玻璃纤维（CV）膜上播种和生物打印，以构建工程 RPE 片。通过截取 RPE 片的特定部分获得的圆形 RPE 片显示出丰富的微绒毛和色素颗粒，同时增殖能力降低，成熟度提高。我们的研究表明，补充小分子和三维球形培养以及生物打印技术是促进 RPE 培养和构建工程 RPE 片的有效方法，可为未来的临床 RPE 细胞治疗和 RPE 模型的研究开发提供支持。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Biological Engineering BIOCHEMICAL RESEARCH METHODS-BIOTECHNOLOGY & APPLIED MICROBIOLOGY

CiteScore

7.10

自引率

1.80%

发文量

审稿时长

17 weeks

期刊介绍： Biological engineering is an emerging discipline that encompasses engineering theory and practice connected to and derived from the science of biology, just as mechanical engineering and electrical engineering are rooted in physics and chemical engineering in chemistry. Topical areas include, but are not limited to: Synthetic biology and cellular design Biomolecular, cellular and tissue engineering Bioproduction and metabolic engineering Biosensors Ecological and environmental engineering Biological engineering education and the biodesign process As the official journal of the Institute of Biological Engineering, Journal of Biological Engineering provides a home for the continuum from biological information science, molecules and cells, product formation, wastes and remediation, and educational advances in curriculum content and pedagogy at the undergraduate and graduate-levels. Manuscripts should explore commonalities with other fields of application by providing some discussion of the broader context of the work and how it connects to other areas within the field.