Establishment of models for retinal regenerative medicine using the eye-like structures from ES cells

利用ES细胞的类眼结构建立视网膜再生医学模型

• 批准号: 15390527
• 负责人: KUNISADA Takahiro
• 金额: $ 10.56万
• 依托单位: Gifu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390527/
• 关键词: ES cells; retina; lens; in vitro differentiation; regenerative medicine; 網膜色素変性症; 細胞療法; レンズ; 試験管内分化; 再生医療

A culture system to generate eye-like structures consisting of lens, neural retina, and retinal pigmented epithelium (RPE) cells from undifferentiated embryonic stem cells has been established. Precursors of RPE cells that differentiated in the cultures were responsive to Wnt2b signaling and identified retrospectively to form secondary colonies consisting of only RPE-like cells in eye-like structures. These transplanted eye-like structures were capable of populating the developing chick eye as neuronal retina and RPE cells. The outgrowth of a single cell layer of mature RPE cells from the grafted eye-like structures confirmed the existence of precursors for RPE cells. These results suggest that the eye-like structures resulted from the normal developmental pathway responsible for generating eyes in vivo. In addition, eye-like structure-derived cells efficiently regenerated injured retinal ganglion cells treated with NMDA, including those extending axons to retinal papilla. If a functional effect of these cells can be established, such eye-like structures may be potentially used to establish therapy models for various eye diseases.

已经建立了一种培养系统，可以从未分化的胚胎干细胞中产生由晶状体、神经视网膜和视网膜色素上皮（RPE）细胞组成的类似眼睛的结构。在培养物中分化的 RPE 细胞前体对 Wnt2b 信号有反应，并经过回顾性鉴定，形成仅由眼状结构中的 RPE 样细胞组成的次生集落。这些移植的类眼结构能够在发育中的鸡眼中形成神经元视网膜和 RPE 细胞。从移植的眼状结构中生长出成熟 RPE 细胞的单细胞层证实了 RPE 细胞前体的存在。这些结果表明，类眼结构是由负责在体内产生眼睛的正常发育途径产生的。此外，眼睛样结构衍生的细胞可以有效地再生经 NMDA 处理的受损视网膜神经节细胞，包括那些将轴突延伸至视网膜乳头的细胞。如果可以确定这些细胞的功能作用，那么这种类似眼睛的结构可能有可能用于建立各种眼部疾病的治疗模型。

项目成果

Embryonic stem cells that differentiate into RPE cell precursors in vitro develop into RPE cell monolayers in vivo.

体外分化为 RPE 细胞前体的胚胎干细胞在体内发育为 RPE 细胞单层。

• 发表时间: 2006
• 作者: Aoki; H.; Hara; A.; Nakagawa; S.; Motohashi; T.; Hirano; M.; Takahashi; Y.; Kunisada; T.
• 通讯作者: T.

Cooperative and indispensable roles of endothelin 3 and KIT signalings in melanocyte development.

内皮素 3 和 KIT 信号在黑素细胞发育中协同且不可或缺的作用。

• 发表时间: 2005
• 作者: Aoki H.; Motohashi; T.; Yoshimura; N.; Yamazaki; H.; Yamane T.; Panthier; J.J.; Kunisada; T
• 通讯作者: T

Embryonic stem cells that differentiate into RPE cell precursors in vitro develop into RPE cell monolayers in vivo.

体外分化为 RPE 细胞前体的胚胎干细胞在体内发育为 RPE 细胞单层。

• 发表时间: 2006
• 作者: Aoki; H.; Hara; A.; Nakagawa; S.; Motohashi; T.; Hirano; M.; Takahashi; Y.; Kunisada; T.
• 通讯作者: T.

Cooperative and indispensable roles of endothelin 3 and KIT signalings in melanocyte development.

内皮素 3 和 KIT 信号在黑素细胞发育中协同且不可或缺的作用。

• 发表时间: 2005
• 作者: Aoki; H.; Motohashi; T.; Yoshimura; N.; Yamazaki; H.; Yamane; T.; Panthier; J.J.; Kunisada; T
• 通讯作者: T

Embryonic stem cells that differentiate into RPE cell precursors in vitro develop into RPE cell monolayers in vivo.

体外分化为 RPE 细胞前体的胚胎干细胞在体内发育为 RPE 细胞单层。

• 发表时间: 2006
• 作者: Aoki; H.; Hara; A.; Nakagawa; S.; Motohashi; T.; Hirano; M.; Takahashi; Y.; Kunisada; T.
• 通讯作者: T.