Comparative Analysis of the Retinal Potential of Embryonic Stem Cells and Amniotic Fluid-Derived Stem Cells

被引：22

作者：

Decembrini, Sarah ^{[1
]}

Cananzi, Mara ^{[1
]}

Gualdoni, Sara ^{[1
]}

Battersby, Alysia ^{[2
]}

Allen, Nick ^{[2
]}

Pearson, Rachael A. ^{[3
]}

Ali, Robin R. ^{[3
]}

De Coppi, Paolo ^{[1
]}

Sowden, Jane C. ^{[1
]}

机构：

[1] Great Ormond St Hosp Sick Children, UCL Inst Child Hlth, London WC1N 1EH, England

[2] UCL Inst Ophthalmol, London, England

[3] Cardiff Univ, Sch Biosci, Cardiff, S Glam, Wales

来源：

STEM CELLS AND DEVELOPMENT | 2011年 / 20卷 / 05期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

HUMAN PLURIPOTENT; PROGENITOR CELLS; SELF-RENEWAL; IN-VITRO; DIFFERENTIATION; TRANSPLANTATION; MOUSE; OCT-3/4; PHOTORECEPTORS; GENERATION;

D O I：

10.1089/scd.2010.0291

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

Photoreceptors have recently been generated from mouse and human embryonic stem cells (ESCs), although ethics concerns impede their utilization for cell replacement therapy for retinal disease. Extra-embryonic tissues have received attention as alternative therapeutic sources of stem cells. Human and mouse amniotic fluid-derived stem cells (AFCs) have been reported to be multipotent and express embryonic and adult stem cell markers. Here, in vitro conditions that generate retinal cells from ESCs were used to analyze and compare the retinal potential of murine AFCs and ESCs. We show that AFCs express pluripotency markers (Nanog, Sox2, and Oct3/4) as well as retinal transcription factor genes (Et, Lhx2, Tll1, Six6, Otx2, Pax6, and Fgf15). AFCs from amniotic fluid of Fgf15.gfp, Nrl.gfp, and Crx.gfp embryos cultured in retinal proliferation and differentiation conditions failed to switch on these retinal transgenes. AFCs cultured in retinal-promoting conditions, effective on ESCs, showed reduced expression of retinal markers. Retinal co-cultures activated retinal genes in ESCs but not in AFCs, and migration assays in retinal explants showed limited migration of AFCs compared with ESCs. Unlike ESCs, AFCs do not express the early embryonic ectodermal gene Utf1 and Western analysis of AFCs identified only the B isoform of Oct3/4, rather than the isoform A present in ESCs. We conclude that AFCs have restricted potential and differ considerably from ESCs and retinal progenitor cells. Reprogramming to induce pluripotency or new differentiation protocols will be required to confer retinal potential to AFCs as expression of a subset of pluripotency and retinal markers is not sufficient.

引用

页码：851 / 863

页数：13

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