Retinal degenerative (RD) diseases that affect photoreceptors and/or retinal pigment epithelium (RPE) affect millions of people worldwide. Stem cell-based therapy is being pursued as a potential approach for those incurable diseases. Our team has assembled expertise in 3 areas: (1) Development of 3D retina organoids (RO’s) from human embryonic stem cells (hESCs) that contain most of the retinal cell types (Dr. Seiler, UCI). When transplanted into immunodeficient RD rats, the RO’s developed lamination, matured into photoreceptors and inner retinal neurons, integrated and restored some visual function. (2a) Our team at USC has developed a unique technique to grow hESC-RPE as a polarized monolayer on ultrathin parylene (hESC-RPE implant) that has functional similarities to a healthy Bruch’s membrane (BM) and is now employed in FDA–approved phase1/2a clinical trials (Dr. Thomas, USC). (2b) The RO sheets can be maintained over the hESC-RPE implants in culture together and can be used as a co-graft for transplantation experiments. Transplantation of RO’s together with polarized RPE supported by an artificial Bruch’s membrane is highly advantageous since the parylene membrane can act as a barrier between the co-graft and the pathological BM surface to prevent BM abnormalities from unfavorably altering the behavior of the transplanted cells. By using this co-graft in an in vitro model system, it is possible to study the influence of RPE on the survival and maturation of RO sheets as required for different disease conditions. (3) By microfluidic bioengineering, capillary networks will be developed by endothelial cells forming an artificial choroid underneath the RPE-retina construct (Dr. Lee, UCI). – This protocol is advantageous because it will combine three different tissue layers of the eye, and can be usable both for drug testing and disease modeling, dependent on the cell source.
Solution for: NEI 3-D Retina Organoid Challenge (3-D ROC)
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