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bioRxiv · 10.1101/2020.11.22.393439

Photoreceptor precursor cell integration into rodent retina after treatment with novel glycopeptide PKX-001

Viringipurampeer, I. A.·Yanai, A.·Gregory-Evans, C. Y.·Gregory-Evans, K.
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Abstract

Cell replacement therapy is emerging as an important approach in novel treatments for neurodegenerative diseases. Many problems remain, in particular improvements are needed in the survival of transplanted cells and increasing functional integration into host tissue. These problems arise because of immune rejection, suboptimal precursor cell type, trauma during cell transplantation, toxic compounds released by dying tissues and nutritional deficiencies. We recently developed an ex vivo system to facilitate identification of factors contributing to the death of transplanted neuronal (photoreceptor) and showed 2.8-fold improvement in transplant cell survival after pre-treatment with a novel glycopeptide (PKC-100). In this study we extended these studies to look at cell survival, maturation and functional integration in an in vivo rat model of rhodopsin-mutant retinitis pigmentosa causing blindness. We found that only when human photoreceptor precursor cells (PPCs) were pre-incubated with PKX-100 prior to transplantation, did the cells integrate and mature into cone photoreceptors expressing S-opsin or L/M opsin. In addition, ribbon synapses were observed in the transplanted cells suggesting they were making synaptic connections with the host tissue. Furthermore, optokinetic tracking and electroretinography responses in vivo were significantly improved compared to cell transplants without PKX-100 pre-treatment. These data demonstrate that PKX-100 promotes significant long-term stem cell survival in vivo, providing a platform for further investigation towards the clinical application to repair damaged or diseased retina.

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Viringipurampeer, I. A., Yanai, A., Gregory-Evans, C. Y., Gregory-Evans, K.. 2020-11-22. Photoreceptor precursor cell integration into rodent retina after treatment with novel glycopeptide PKX-001. https://doi.org/10.1101/2020.11.22.393439

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