Beijing Tongren Hospital, Capital Medical University, Beijing, China (People's Republic)
Abstract: Cell therapy, a cornerstone of regenerative medicine, involves transplanting cells to replace damaged tissues. Recent advancements in treating retinal degeneration through RPE cell replacement have shown promise, but these cells can only provide early intervention or nutritional support. Photoreceptor cells, which are specialized for light-sensing, face challenges in surviving and integrating after transplantation due to the host microenvironment, limiting their therapeutic efficacy. To address this, the concept of photoreceptor cell co-transplantation was proposed. In this approach, two types of cells are utilized: the primary cell source-photoreceptor cells, which replace the degenerated photoreceptor cells of retinal degeneration; sub-cell source -X cells, that support the primary cell source for efficient transplantation and improved post-transplant survival. Therefore, whether the combined transplantation of well-functioning X cells can enhance the subretinal microenvironment, thereby promoting the survival and integration of transplanted photoreceptor cells and improving overall transplantation efficiency, is a critical scientific question that this study aims to address. In our previous studies, we have developed techniques to efficiently differentiate human pluripotent stem cells (hiPSCs) into X cells and retinal organoids (ROs) to obtain photoreceptor precursor cells. We also established an humanized immunodeficient mouse model of retinal degeneration (Rd10-MRG) suitable for X cell transplantation. Significant progress has been made in treating Rd10-MRG through the co-transplantation of X cells and photoreceptor cells. Experimental results indicate that co-transplantation enhances the survival and integration of photoreceptor cells compared to single-cell type transplantation, leading to improved functional and structural outcomes in the host retina. However, further molecular biology experiments are required to elucidate the underlying mechanisms. It is anticipated that this combined cell transplantation approach will offer novel insights and strategies for the treatment of retinal degenerative diseases.
