Induced pluripotent stem cell-based therapy for age-related macular degeneration

ABSTRACT

Introduction: In age-related macular degeneration (AMD), stem cells could possibly replace or regenerate disrupted pathologic retinal pigment epithelium (RPE), and produce supportive growth factors and cytokines such as brain-derived neurotrophic factor.  Induced pluripotent stem cells (iPSCs)-derived RPE was first subretinally transplanted in a neovascular AMD patient in 2014.

Areas covered: Induced PSCs are derived from the introduction of transcription factors to adult cells under specific cell culture conditions, followed by differentiation into RPE cells. Induced PSC-derived RPE cells exhibit ion transport, membrane potential, polarized VEGF secretion and gene expression that is similar to native RPE. Despite having similar in vitro function, morphology, immunostaining and microscopic analysis, it remains to be seen if iPSC-derived RPE can replicate the myriad of in vivo functions, including immunomodulatory effects, of native RPE cells.  Historically, adjuvant RPE transplantation during CNV resections were technically difficult and complicated by immune rejection. Autologous iPSCs are hypothesized to reduce the risk of immune rejection, but their production is time-consuming and expensive.  Alternatively, allogenic transplantation using human leukocyte antigen (HLA)-matched iPSCs, similar to HLA-matched organ transplantation, is currently being investigated.

Expert opinion: Challenges to successful transplantation with iPSCs include surgical technique, a pathologic subretinal microenvironment, possible immune rejection, and complications of immunosuppression.

KEYWORDS:

• Induced pluripotent stem cell
• stem cell
• non-neovascular age-related macular degeneration
• neovascular age-related macular degeneration

Article highlights

• In both neovascular and advanced non-neovascular age-related macular degeneration (AMD), stem cell therapy has the potential to improve on current therapeutic limitations.

• Induced pluripotent stem cells (iPSCs) are promising in that they are derived from adult human cells, ameliorating the need for embryonic stem cells (ESCs) and have the potential for reduced immunogenicity.

• Retinal pigment epithelial (RPE) tissue, derived from iPSCs, has undergone the most extensive research in AMD therapy and holds the most promise for application in humans.

• Previous studies investigating adjuvant RPE transplantation combined with choroidal neovascular membrane resection have provided excellent lessons for the application of iPSC-based therapies.

• The use of iPSCs was first performed on a Japanese female with end-stage AMD, and this marked a major milestone as the first application of an iPSC-based therapy in humans.

• Significantly more research is needed to determine the efficacy and safety of transplantation of stem cells in AMD.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This manuscript has not been funded.