Retinal Cell Transplantation, Biomaterials, and In Vitro Models for Developing Next-generation Therapies of Age-related Macular Degeneration

Abstract

Retinal pigment epithelium (RPE) cells grown on a scaffold, an RPE patch, have potential to ameliorate visual impairment in a limited number of retinal degenerative conditions. This tissue-replacement therapy is suited for age-related macular degeneration (AMD), and related diseases. RPE cells must be transplanted before the disease reaches a point of no return, represented by the loss of photoreceptors. Photoreceptors are specialized, terminally differentiated neurosensory cells that must interact with RPE’s apical processes to be functional. Human photoreceptors are not known to regenerate. On the RPE’s basal side, the RPE transplant must induce the reformation of the choriocapillaris, thereby re-establishing the outer blood-retinal barrier. Because the scaffold is positioned between the RPE and choriocapillaris, it should ideally degrade and be replaced by the natural extracellular matrix that separates these tissues. Besides biodegradable, the scaffolds need to be nontoxic, thin enough to not affect the focal length of the eye, strong enough to survive the transplant procedure, yet flexible enough to conform to the curvature of the retina. The challenge is patients with progressing AMD treasure their remaining vision and fear that a risky surgical procedure will further degrade their vision. Accordingly, clinical trials only treat eyes with severe impairment that have few photoreceptors to interact with the transplanted patch. Although safety has been demonstrated, the cell-replacement mechanism and efficacy remain difficult to validate. This review covers the structure of the retina, the pathology of AMD, the limitations of cell therapy approaches, and the recent progress in developing retinal therapies using biomaterials.

Cell‐instructive biomaterials in tissue engineering and regenerative medicine

“…for more extensive information on tissue engineering applications for retinal regeneration. 42,43 3 | SKIN/WOUND HEALING…”

“…We direct the readers to recent reviews by Sakpal et. al and Rizzolo et al for more extensive information on tissue engineering applications for retinal regeneration 42,43 …”

Cell Sources for Retinal Regeneration: Implication for Data Translation in Biomedicine of the Eye

“…In this regard, and taking into account the common origin of RPE and NR in the development of the eye and the possibility of their mutual conversion [ 39 ], RPE has been extensively studied using animal models and in humans. Studies have been conducted in various directions: cell functions, differentiation of RPE and its changes during regeneration, and congenital and acquired eye pathologies; RPE behavior in vitro and under transplantation conditions has also been investigated [ 127 , 130 , 131 , 132 , 133 , 134 , 135 , 136 ].…”

Determining the optimal stage for cryopreservation of human embryonic stem cell-derived retinal pigment epithelial cells

“…The safety and efficacy of cell-replacement therapy as a treatment for retinal degenerative diseases are being tested in phase I/II clinical trials using hESC-derived RPE [ 5 – 8 ] (for more information, visit http://www.clinicaltrials.gov ). To date, much emphasis has been placed on developing methods to differentiate hESCs to RPE, the best delivery strategy, and the development of scaffolds for RPE transplantation [ 9 – 13 ]. However, research on RPE cryopreservation to preserve post-thaw function is still limited.…”

“…gov). To date, much emphasis has been placed on developing methods to differentiate hESCs to RPE, the best delivery strategy, and the development of scaffolds for RPE transplantation [9][10][11][12][13]. However, research on RPE cryopreservation to preserve post-thaw function is still limited.…”