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在 3D 培养系统中整合顶端乳头的干细胞可提高人胚胎干细胞来源的视网膜类器官的形成。

Integrated stem cells from apical papilla in a 3D culture system improve human embryonic stem cell derived retinal organoid formation.

机构信息

Department of Biology, University of Payam Noor, Isfahan, Iran; Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.

Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.

出版信息

Life Sci. 2022 Feb 15;291:120273. doi: 10.1016/j.lfs.2021.120273. Epub 2022 Jan 10.

DOI:10.1016/j.lfs.2021.120273
PMID:35016877
Abstract

AIM

Eye organoids are 3D models of the retina that provide new possibilities for studying retinal development, drug toxicity and the molecular mechanisms of diseases. Although there are several protocols that can be used to generate functional tissues, none have been used to assemble human retinal organoids containing mesenchymal stem cells (MSCs).

MAIN METHODS

In this study we intend to assess the effective interactions of MSCs and human embryonic stem cells (hESCs) during retinal organoid formation. We evaluated the inducing activities of bone marrow MSCs (BM-MSCs), trabecular meshwork (TM), and stem cells from apical papilla (SCAP)-derived MSCs in differentiation of hESCs in a three-dimensional (3D) direct co-culture system.

KEY FINDINGS

In comparison with the two other MSC sources, the induction potential of SCAP was confirmed in the co-culture system. Although the different SCAP cell ratios did not show any significant morphology changes during the first seven days, increasing the number of SCAPs improved formation of the optic vesicle (OV) structure, which was confirmed by assessment of specific markers. The OVs subsequently developed to an optic cup (OC), which was similar to the in vivo environment. These arrangements expressed MITF in the outer layer and CHX10 in the inner layer.

SIGNIFICANCE

We assessed the inducing activity of SCAP during differentiation of hESCs towards a retinal fate in a 3D organoid system. However, future studies be conducted to gather additional details about the development of the eye field, retinal differentiation, and the molecular mechanisms of diseases.

摘要

目的

眼类器官是视网膜的 3D 模型,为研究视网膜发育、药物毒性和疾病的分子机制提供了新的可能性。虽然有几种可以用来生成功能性组织的方案,但没有一种方案被用于组装包含间充质干细胞(MSCs)的人视网膜类器官。

主要方法

在这项研究中,我们打算评估 MSC 和人胚胎干细胞(hESCs)在视网膜类器官形成过程中的有效相互作用。我们评估了骨髓间充质干细胞(BM-MSCs)、小梁网(TM)和来源于顶端乳头的干细胞(SCAP)衍生的 MSC 在三维(3D)直接共培养系统中诱导 hESC 分化的活性。

主要发现

与其他两种 MSC 来源相比,SCAP 在共培养系统中的诱导潜能得到了证实。尽管不同的 SCAP 细胞比例在前七天没有显示出任何明显的形态变化,但增加 SCAP 的数量可以改善视囊(OV)结构的形成,这通过评估特定标志物得到了证实。随后,OV 发育成类似于体内环境的视杯(OC)。这些排列在外层表达 MITF,在内层表达 CHX10。

意义

我们评估了 SCAP 在 hESC 向 3D 类器官系统中的视网膜命运分化过程中的诱导活性。然而,未来的研究需要进一步收集关于眼区发育、视网膜分化和疾病分子机制的详细信息。

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