Retinal therapy with induced pluripotent stem cells; leading the way to human clinical trials

ABSTRACT

Introduction: Retinal cell transplantation is a promising approach to delay progression and reverse blindness caused by infections, genetic inheritance, or associated with aging.

Areas covered: The demand for transplantable retinal cells is broad and several cell sources exist that can supply such cells. The recent development of protocols that reprogram adult cells to their pluripotent potential (induced pluripotent stem cells; iPSCs) and the possibility of differentiating iPSCs to many retinal types make these cells very attractive for cell therapeutics in the degenerating retina.iPSCs overcome ethical dilemmas in using fetal cells and with autologous transplantation of iPSC derived retinal cells, immunosuppression will no longer be needed. Importantly, gene editing of iPSCs derived from patients with genetic diseases will allow autologous transplantation of healthy differentiated retinal cells.

Expert commentary: Before marketing clinically useful retinal cells, differentiated from iPSCs, a multistep clinical trial is performed. Currently, 23 trials are described in the literature and they report no adverse reactions to cell transplantation. Early visual assessment tests demonstrate small visual benefits in a proportion of participants, with future results anticipated in the near future.

KEYWORDS:

• Retinal degeneration
• cell replacement therapy
• human induced pluripotent stem cells
• animal models
• clinical trials

Key issues

• With aging population on the rise and the resulting increase in the number of people with visual impairment, affecting many aspects of individual’s lifestyle, an urgent need exists for clinical grade cells that can replace dying cells in the retina.

• The generation of cells that can be reprogrammed to their pluripotent potential from fully differentiated cells (iPSCs) and their subsequent differentiation to several retinal cell types has made cell therapy a feasible treatment option for the visually impaired.

• Improved differentiation protocols and selection methods are now enabling the production of cell population enriched with specific cell types (i.e. photoreceptors).

• Further improvements in protocols for mass production of clinical grade differentiated retinal cells, combined with better solutions to tackle difficulties such as immune rejection is making retinal cell transplantation a realistic goal.

Declaration of interest

K. Gregory-Evans reports receiving financial support from Protokinetix Inc. and the Canadian Institute of Health. A. Yanai reports receiving financial support from the Canadian Institute of Health. The authors have no other 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.