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Transplantation of iPS-derived Human Photoreceptor Cells Successfully Integrated into The Retina and Restored Rhe Photoreceptor Ability of Mice

Studies have shown that the human brain mainly receives external information through five senses: vision, hearing, smell, touch and taste, of which at least 80% of the external information is obtained through vision. Therefore, the loss of vision is a very bad and terrible thing for people. It not only brings a lot of inconvenience to the blind person's life, but also severely affects the spiritual belief of the blind person.

For a long time, it has been extremely difficult to treat blindness, and there has been a lack of effective methods to treat blindness in clinical practice. Transplanting photoreceptor cells is a promising treatment that could help restore vision in people with blinding diseases in the future. Recently, a research team from the University of Dresden in Germany produced a large number of iPS-based human photoreceptor cells in vitro, and then transplanted them into the mouse retina. The experimental results showed that these human photoreceptor cells can be integrated into the degenerated mouse retina in large quantities, and re-perceived light in visually impaired mice.

This is the first time that transplanted photoreceptor cells have been integrated into the retina on such a large scale, and represents a new breakthrough in the treatment of blinding diseases by transplanting photoreceptor cells.

In order to increase the integration efficiency after photoreceptor cell transplantation, the research team performed several optimizations, and they found that the "age" of the transplanted photoreceptor cells was a key factor in the integration efficiency. Both "younger" and "older" photoreceptor cells were significantly less efficient at integrating into the retina after transplantation. They also found that it took a long time for these photoreceptor cells to integrate into the retina, up to 6 months, before they could establish a network of interactions with other cells in the retina to achieve integration.

Furthermore, the interaction of these transplanted photoreceptor cells with other undamaged cells in the retina is another key factor for successful integration. About 30% of the cells in the retina support photoreceptor work. In this study, it was clearly seen that the interaction of transplanted photoreceptor cells with host retinal cells is critical for successful integration and developmental maturation.

The research team first used human induced pluripotent stem cells (iPSCs) to grow retinal organoids in laboratory dishes, harvested and used for transplantation when these retinal organoids had reached the appropriate stage of development.

Obtaining purer photoreceptor cells was a challenge for this study, and to address this, the research team developed a new stem cell line using the piggyBac transposon system to generate the expression of the cone-specific mouse cone arrestin (mCar). ) hiPSC cell line carrying green fluorescent protein (GFP) under the control of the promoter. The addition of these labels enables efficient isolation of desired photoreceptor cells from cultured retinal organoids without affecting cell function. Moreover, this induced pluripotent stem cell line provides an almost unlimited source of photoreceptor cells, laying the foundation for future large-scale clinical applications.

Next, the research team studied mice with partially degenerated retinas that had damaged cones in two types of photoreceptor cells, but normal rods. Cone cells mainly perceive bright light, photopic vision, and color vision, while rod cells mainly perceive low light, scotopic vision, and vision without color. The research team transplanted the cultured and purified photoreceptor cells into mice with damaged cone cells. The experimental results showed that these transplanted photoreceptor cells could successfully integrate into the mouse retina and develop into normal photoreceptors. Downstream nerve cells in the retina transmit signals that restore light sensitivity in mice.

This preclinical study suggests that transplanting photoreceptor cells in the retina before they have completely degenerated in patients with blinding diseases is a potential approach to restore vision.

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