Scaffolds for cell transplantation

Dry age-related macular degeneration (AMD) is the most common cause of blindness in the elderly and is thought to result from dysfunction and loss of retinal pigmented epithelium (RPE) resulting in photoreceptor loss. Replacement of lost RPE cells with stem cell-derived RPE (SC-RPE) in patients with AMD and similar retinal diseases is currently being tested in clinical trials. Subretinal delivery of cell suspensions of SC-RPE is being investigated as a treatment approach. However, there are concerns about long-term survival of these cells and their ability to form a polarized monolayer, which is vital for RPE function. Implantation of SC-RPE cells grown on natural or synthetic bioengineered scaffolds made of biodegradable or nonbiodegradable materials has resulted in promising anatomic and functional outcomes in preclinical studies. Such scaffolds support the survival and function of the RPE monolayer and facilitate manipulation and subretinal implantation. An ideal scaffold should mimic the properties of the natural RPE substrate: Bruch's membrane. It should have a similar thickness, flexibility, micro- and macromolecule permeability, and the ability to promote survival, polarity, and function of the transplanted SC-RPE. Here, we discuss the rationale for using scaffolds in retinal cell replacement therapies. We focus on RPE scaffold materials that have been investigated in preclinical studies, as well as those that have already been clinically tested. Scaffold materials for the transplantation of neural retinal cells are also reviewed. The chapter concludes by describing future challenges for retinal cell therapies using scaffolds, and approaches that will lead to optimal outcomes.