Embryonic stem cells and retinal repair

Abstract

In this review we examine the potential of embryonic stem cells (ESCs) for use in the treatment of retinal diseases involving photoreceptors and retinal pigment epithelium (RPE). We outline the ontogenesis of target retinal cell types (RPE, rods and cones) and discuss how an understanding of developmental processes can inform our manipulation of ESCs in vitro. Due to their potential for cellular therapy, special emphasis is placed upon the derivation and culture of human embryonic stem cells (HESCs) and their differentiation towards a retinal phenotype. In terms of achieving this goal, we suggest that much of the success to date reflects permissive in vitro environments provided by established protocols for HESC derivation, propagation and neural differentiation. In addition, we summarise key factors that may be important for enhancing efficiency of retinal cell-type derivation from HESCs. The retina is an amenable component of the central nervous system (CNS) and as such, diseases of this structure provide a realistic target for the application of HESC-derived cellular therapy to the CNS. In order to further this goal, the second component of our review focuses on the cellular and molecular cues within retinal environments that may influence the survival and behaviour of transplanted cells. Our analysis considers both the potential barriers to transplant integration in the retina itself together with the remodelling in host visual centres that is known to accompany retinal dystrophy.

Generation of V2a Interneurons from Mouse Embryonic Stem Cells

“…The Chx10 transcription factor is also present in photoreceptor progenitor cells [38]. The protocol to differentiate this cell type uses low concentrations of RA [45].…”

“…The effect of varying the level of Shh signaling on the expression of transcription factors expressed in p2 progenitors and V2a interneurons was also determined. Since Chx10 is also expressed in photoreceptor progenitor cells, the absence of another photoreceptor progenitor marker (Crx) was used to confirm the spinal fate of the induced cells [37,38]. Inhibition of the Notch-1 signaling was also evaluated to determine the effect of Notch signaling on the number of Chx10 + V2a interneurons and Gata3 + V2b interneurons.…”

Proliferation and Pluripotency of Human Embryonic Stem Cells Maintained on Type I Collagen

“…These cells could also provide a source of cellular therapies for the replacement of damaged or destroyed tissues [10][11][12][13][14][15], and tissues derived from hESC could be used in drug discovery and toxicology studies [16,17]. The success of these applications, however, depends on our capacity to provide an adequate supply of hESC for research and development purposes.…”

Strategies for retinal cell generation from human pluripotent stem cells

“…For more than a decade, RPE have been generated from pluripotent stem cells by spontaneous differentiate upon removal of basic fibroblast growth factor (bFGF) from the cell culture medium (25)(26)(27)(28)(29)(30)(31)(32). Gene expression profiling asserted the quantitative similarity between RPE generated using this strategy and human fetal RPE.…”