Directed Differentiation of Human Embryonic Stem Cells into Functional Retinal Pigment Epithelium Cells

被引：354

作者：

Idelson, Maria ^{[1
,2
]}

Alper, Ruslana ^{[4
]}

Obolensky, Alexey ^{[4
]}

Ben-Shushan, Etti ^{[1
,2
]}

Hemo, Itzhak ^{[4
]}

Yachimovich-Cohen, Nurit ^{[1
,2
]}

Khaner, Hanita ^{[1
,2
]}

Smith, Yoav ^{[3
]}

Wiser, Ofer ^{[5
]}

Gropp, Michal ^{[1
,2
]}

Cohen, Malkiel A. ^{[1
,2
]}

Even-Ram, Sharona ^{[1
,2
]}

Berman-Zaken, Yael ^{[1
,2
]}

Matzrafi, Limor ^{[5
]}

Rechavi, Gideon ^{[6
,7
]}

Banin, Eyal ^{[4
]}

Reubinoff, Benjamin ^{[1
,2
]}

机构：

[1] Hadassah Hebrew Univ Med Ctr, Goldyne Savad Inst Gene Therapy, Hadassah Human Embryon Stem Cell Res Ctr, IL-91120 Jerusalem, Israel

[2] Hadassah Hebrew Univ Med Ctr, Dept Gynecol, IL-91120 Jerusalem, Israel

[3] Hadassah Hebrew Univ Med Ctr, Genom Data Anal Unit, IL-91120 Jerusalem, Israel

[4] Hadassah Hebrew Univ Med Ctr, Ctr Retinal & Macular Degenerat, Dept Ophthalmol, IL-91120 Jerusalem, Israel

[5] CellCure Neurosci Ltd, IL-91120 Jerusalem, Israel

[6] Chaim Sheba Med Ctr, Pediat Hematooncol Dept, IL-52621 Tel Aviv, Israel

[7] Chaim Sheba Med Ctr, Inst Hematol, IL-52621 Tel Aviv, Israel

来源：

CELL STEM CELL | 2009年 / 5卷 / 04期

基金：

以色列科学基金会;

关键词：

RCS RATS; PHOTORECEPTOR DEGENERATION; EYE DEVELOPMENT; VISUAL FUNCTION; NICOTINAMIDE; TRANSPLANTATION; PRESERVATION; CONTRIBUTES; INHIBITOR; LONGEVITY;

D O I：

10.1016/j.stem.2009.07.002

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Dysfunction and loss of retinal pigment epithelium (RPE) leads to degeneration of photoreceptors in age-related macular degeneration and subtypes of retinitis pigmentosa. Human embryonic stem cells (hESCs) may serve as an unlimited source of RPE cells for transplantation in these blinding conditions. Here we show the directed differentiation of hESCs toward an RPE fate under defined culture conditions. We demonstrate that nicotinamide promotes the differentiation of hESCs to neural and subsequently to RPE fate. In the presence of nicotinamide, factors from the TGF-beta superfamily, which presumably pattern RIDE development during embryogenesis, further direct RPE differentiation. The hESC-derived pigmented cells exhibit the morphology, marker expression, and function of authentic RPE and rescue retinal structure and function after transplantation to an animal model of retinal degeneration caused by RPE dysfunction. These results are an important step toward the future use of hESCs to replenish RPE in blinding diseases.

引用

页码：396 / 408

页数：13

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