Stem Cell Therapies in Retinal Disorders.

Aakriti Garg,Stephen Tsang,Winston Lee,Jin Yang

doi:10.3390/cells6010004

Aakriti Garg, Stephen Tsang + Show 2 more

Open Access

https://doi.org/10.3390/cells6010004

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Abstract

Stem cell therapy has long been considered a promising mode of treatment for retinal conditions. While human embryonic stem cells (ESCs) have provided the precedent for regenerative medicine, the development of induced pluripotent stem cells (iPSCs) revolutionized this field. iPSCs allow for the development of many types of retinal cells, including those of the retinal pigment epithelium, photoreceptors, and ganglion cells, and can model polygenic diseases such as age-related macular degeneration. Cellular programming and reprogramming technology is especially useful in retinal diseases, as it allows for the study of living cells that have genetic variants that are specific to patients’ diseases. Since iPSCs are a self-renewing resource, scientists can experiment with an unlimited number of pluripotent cells to perfect the process of targeted differentiation, transplantation, and more, for personalized medicine. Challenges in the use of stem cells are present from the scientific, ethical, and political realms. These include transplant complications leading to anatomically incorrect placement, concern for tumorigenesis, and incomplete targeting of differentiation leading to contamination by different types of cells. Despite these limitations, human ESCs and iPSCs specific to individual patients can revolutionize the study of retinal disease and may be effective therapies for conditions currently considered incurable.

Highlights

Stem Cell TransplantationStem cell therapy has long been considered a promising mode of treatment for retinal conditions.Human embryonic stem cells were once considered the only promising source of replacement cells in regenerative medicine
The development of induced pluripotent stem cells (iPSCs) allowed for a source of retinal cells for transplantation, much more cost-effective methods of drug testing, and the development of models that, at times, mimic human disease better than animal models, which do not always have physiology that is comparable to humans
In 2007, Takahashi et al published a method describing the creation of iPSCs, skin fibroblasts were first transduced with viral constructs expressing four transcription factors—octamer-binding transcription factor 4 (OCT4), sex-determining region Y-box 2 (SOX2), Krüppel-like factor 4 (KLF4), and C-MYC [8,9,10,11]—that allowed mature cells to return to a pluripotent state similar to that seen in embryonic stem cells (ESCs) [10]

Summary

Introduction

Stem cell therapy has long been considered a promising mode of treatment for retinal conditions. The blood–ocular barrier protects the subretinal space by antigen-specific inhibition of responses of cellular and humoral immune systems, provided that it is not physically compromised during transplantation or due to the underlying disease pathology [2]. In such cases, the immunogenicity remains a challenge in hESC-derived transplantation, but can be mitigated. The development of iPSCs allowed for a source of retinal cells for transplantation, much more cost-effective methods of drug testing, and the development of models that, at times, mimic human disease better than animal models, which do not always have physiology that is comparable to humans. In 2007, Takahashi et al published a method describing the creation of iPSCs, skin fibroblasts were first transduced with viral constructs expressing four transcription factors—OCT4, SOX2, Krüppel-like factor 4 (KLF4), and C-MYC [8,9,10,11]—that allowed mature cells to return to a pluripotent state similar to that seen in ESCs [10]

Success of iPSCs

Stem Cells and Retinal Conditions

Modeling Retinal Diseases in a Dish

Limitations of Stem Cell Use

Findings

Conclusions