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.

建立了一个由未分化的胚胎干细胞产生晶状体、神经视网膜和视网膜色素上皮（RPE）细胞的眼样结构的培养系统。在培养中分化的RPE细胞前体对Wnt2b信号有反应，并回顾性地鉴定为形成仅由眼状结构的RPE样细胞组成的继代集落。这些移植的眼样结构能够以神经元视网膜和RPE细胞的形式填充发育中的小鸡眼。移植的眼样结构中成熟RPE细胞的单层生长证实了RPE细胞前体的存在。这些结果表明，眼样结构是由正常的发育途径导致的，负责在体内产生眼睛。此外，类眼结构来源的细胞可以有效地再生NMDA处理的受损视网膜神经节细胞，包括那些延伸轴突到视网膜乳头的细胞。如果能够确定这些细胞的功能作用，这种类眼结构可能潜在地用于建立各种眼病的治疗模型。

项目成果

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

• DOI: 10.1016/j.exer.2005.06.021
• 发表时间: 2006-02-01
• 期刊: EXPERIMENTAL EYE RESEARCH
• 影响因子: 3.4
• 作者: Aoki, H;Hara, A;Kunisada, T
• 通讯作者: Kunisada, T

國貞隆弘: "ES細胞から誘導された眼様構造"再生医療. 2. 59-63 (2003)

Takahiro Kunisada：“源自 ES 细胞的眼状结构”再生医学 2. 59-63 (2003)。

培養細胞実験ハンドブック

培养细胞实验手册

• 发表时间: 2004
• 作者: Yoshida;A.;手塚 建一
• 通讯作者: 手塚 建一

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

• DOI: 10.1002/dvdy.20340
• 发表时间: 2005-06-01
• 期刊: DEVELOPMENTAL DYNAMICS
• 影响因子: 2.5
• 作者: Aoki, H;Motohashi, T;Kunisada, T
• 通讯作者: Kunisada, T

Hara A.: "Embryonic stem cells are capable of generating a neuronal network in the adult mouse retina"Brain Res.. 999. 216-221 (2004)

Hara A.：“胚胎干细胞能够在成年小鼠视网膜中生成神经元网络”Brain Res.. 999. 216-221 (2004)