Small Molecule Mediated Proliferation of Primary Retinal Pigment Epithelial Cells

被引：8

作者：

Swoboda, Jonathan G. ^{[1
,2
]}

Elliott, Jimmy ^{[3
]}

Deshmukh, Vishal ^{[1
,2
]}

de Lichtervelde, Lorenzo ^{[1
,2
]}

Shen, Weijun ^{[4
]}

Tremblay, Matthew S. ^{[4
]}

Peters, Eric C. ^{[3
]}

Cho, Charles Y. ^{[3
]}

Lu, Bin ^{[5
]}

Girman, Sergej ^{[5
]}

Wang, Shaomei ^{[5
]}

Schultz, Peter G. ^{[1
,2
]}

机构：

[1] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

[3] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA

[4] Calif Inst Biomed Res, La Jolla, CA 92037 USA

[5] Cedars Sinai Med Ctr, Regenerat Med Inst, Los Angeles, CA 90048 USA

来源：

ACS CHEMICAL BIOLOGY | 2013年 / 8卷 / 07期

基金：

美国国家卫生研究院;

关键词：

EMBRYONIC STEM-CELLS; MACULAR DEGENERATION; VISUAL FUNCTION; IN-VITRO; RCS RATS; RPE; TRANSPLANTATION; CULTURE; SURVIVAL; THERAPY;

D O I：

10.1021/cb4001712

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Retinal pigment epithelial (RPE) cells form a monolayer adjacent to the retina and play a critical role in the visual light cycle. Degeneration of RPE cells results in retinal disorders such as age-related macular degeneration. Cell transplant strategies have potential therapeutic value for such disorders; however, risks associated with an inadequate supply of donor cells limit their therapeutic success. The identification of factors that proliferate RPE cells ex vivo could provide a renewable source of cells for transplantation. Here, we report that a small molecule (WS3) can reversibly proliferate primary RPE cells isolated from fetal and adult human donors. Following withdrawal of WS3, RPE cells differentiate into a functional monolayer, as exhibited by their expression of mature RPE genes and phagocytosis of photoreceptor outer segments. Furthermore, chemically expanded RPE cells preserve vision when transplanted into dystrophic Royal College of Surgeons (RCS) rats, a well-established model of retinal degeneration.

引用

页码：1407 / 1411

页数：5

共 31 条

[1] Induction of Differentiation by Pyruvate and DMEM in the Human Retinal Pigment Epithelium Cell Line ARPE-19 [J].

Ahmado, Ahmad ;

Carr, Amanda-Jayne ;

Vugler, Anthony A. ;

Semo, Ma'ayan ;

Gias, Carlos ;

Lawrence, Jean M. ;

Chen, Li Li ;

Chen, Fred K. ;

Turowski, Patric ;

da Cruz, Lyndon ;

Coffey, Peter J. .

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2011, 52 (10) :7148-7159

[2] Neurally selected embryonic stem cells induce tumor formation after long-term survival following engraftment into the subretinal space [J].

Arnhold, S ;

Klein, H ;

Semkova, I ;

Addicks, K ;

Schraermeyer, U .

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2004, 45 (12) :4251-4255

[3]

ARONSON JF, 1983, IN VITRO CELL DEV B, V19, P642

[4] Naturally occurring animal models with outer retina phenotypes [J].

Baehr, Wolfgang ;

Frederick, Jeanne M. .

VISION RESEARCH, 2009, 49 (22) :2636-2652

[5] Derivation of Functional Retinal Pigmented Epithelium from Induced Pluripotent Stem Cells [J].

Buchholz, David E. ;

Hikita, Sherry T. ;

Rowland, Teisha J. ;

Friedrich, Amy M. ;

Hinman, Cassidy R. ;

Johnson, Lincoln V. ;

Clegg, Dennis O. .

STEM CELLS, 2009, 27 (10) :2427-2434

[6] Clinical scale ex vivo expansion of cord blood-derived outgrowth endothelial progenitor cells is associated with high incidence of karyotype aberrations [J].

Corselli, Mirko ;

Parodia, Alessia ;

Mogni, Massimo ;

Sessarego, Nadia ;

Kunkl, Annalisa ;

Dagna-Bricarelli, Franca ;

Ibatici, Adalberto ;

Pozzi, Sarah ;

Bacigalupo, Andrea ;

Frassoni, Francesco ;

Piaggio, Giovanna .

EXPERIMENTAL HEMATOLOGY, 2008, 36 (03) :340-349

[7] Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat [J].

D'Cruz, PM ;

Yasumura, D ;

Weir, J ;

Matthes, MT ;

Abderrahim, H ;

LaVail, MM ;

Vollrath, D .

HUMAN MOLECULAR GENETICS, 2000, 9 (04) :645-651

[8] Time course of deterioration of rod and cone function in RCS rat and the effects of subretinal cell grafting: a light- and dark-adaptation study [J].

Girman, S ;

Wang, S ;

Lund, RD .

VISION RESEARCH, 2005, 45 (03) :343-354

[9] Culture of human retinal pigment epithelial cells from peripheral scleral flap biopsies [J].

Ishida, M ;

Lui, GM ;

Yamani, A ;

Sugino, IK ;

Zarbin, MA .

CURRENT EYE RESEARCH, 1998, 17 (04) :392-402

[10] Minimum number of adult human retinal pigment epithelial cells required to establish a confluent monolayer in vitro [J].

Kim, KS ;

Tezel, TH ;

Del Priore, LV .

CURRENT EYE RESEARCH, 1998, 17 (10) :962-969

← 1 2 3 4 →