Stem Cells for Retinal Replacement Therapy

Abstract

Retinal degenerative disease has limited therapeutic options and the possibility of stem cell-mediated regenerative treatments is being actively explored for these blinding retinal conditions. The relative accessibility of this central nervous system tissue and the ability to visually monitor changes after transplantation make the retina and adjacent retinal pigment epithelium prime targets for pioneering stem cell therapeutics. Prior work conducted for several decades indicated the promise of cell transplantation for retinal disease, and new strategies that combine these established surgical approaches with stem cell-derived donor cells is ongoing. A variety of tissue-specific and pluripotent-derived donor cells are being advanced to replace lost or damaged retinal cells and/or to slow the disease processes by providing neuroprotective factors, with the ultimate aim of long-term improvement in visual function. Clinical trials are in the early stages, and data on safety and efficacy are widely anticipated. Positive outcomes from these stem cell-based clinical studies would radically change the way that blinding disorders are approached in the clinic.

Stem cell therapy for retinal diseases

“…The hESC RPE not only display consistent structure with adult RPE, but also exhibit resemblances, as the ability to phagocytes photoreceptor outer segments. The hESC RPE in animals improved functional performance, after comparing with controls, and significant similarity compared to what is found in adult humans [6,8,9] . The United States FDA recently approved a Ⅰ/Ⅱ clinical trial, currently ongoing with hESC, for the treatment of GA and Stargardt's macular dystrophy [7,19] .…”

“…Possibility of teratomas, management of immune rejection and histocompatibility with the hESC, turns it into a difficult clinical application [11][12][13] . The iPSC is an interesting alternative to avoid immune rejection, but it is important to point out that iPSC may become imunnogenic after reprogramming [4,6,8,21] . It is predictable that the "autogenous" iPSC RPE transplantation could improve results in patients with retinal degeneration [16] .…”

“…Several groups have demonstrated successful photoreceptors' transplantations in animals, performing synaptic connections between grafts and host retina, and significant functional improvements [2,22] . Retinal SC (RSC) has been cultured from the peripheral mammalian retina [6] . RSC transplanted subretinally into animal models develop into photoreceptors after integration, with long term survival [2,6] .…”

“…However, the inner retina remains intact, becoming suitable to the possibility of photoreceptors replacement as a potential therapy [2] . Therapeutic options that could substitute affected retinal layers, aim to replace lost or injured retinal components, and reestablish the interaction concerning RPE and photoreceptors [2,5,6] . Autologous full thickness grafts have been used most commonly in humans, but the pursuit for the best method to replace RPE is still ongoing [7] .…”

Differentiation of Pluripotent Stem Cells into Retinal Pigmented Epithelium

“…While many excellent reviews have been written on this topic [47,[50][51][52], the field is developing fast enough to warrant a new discussion.…”