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However, preclinical studies performed in animal models at the early stage of disease do not optimally translate to patients that present to the clinic at a later stage of disease. As the retina degenerates, inflammation and oxidative stress increase and trophic factor support declines. Testing stem cell therapies in animal models at a clinically relevant stage is critical for translation to the clinic. Human neural progenitor cells (hNPC) and hNPC engineered to stably express GDNF (hNPCGDNF) were subretinally injected into the Royal College of Surgeon (RCS) rats, a well-established model for retinal degeneration, at early and later stages of the disease. hNPCGDNF treatment at the early stage of retinal degeneration provided enhanced visual function compared to hNPC alone. Treatment with both cell types resulted in preserved retinal morphology compared to controls. hNPCGDNF treatment led to significantly broader photoreceptor protection than hNPC treatment at both early and later times of intervention. The phagocytic role of hNPC appears to support RPE cell functions and the secreted GDNF offers neuroprotection and enables the extended survival of photoreceptor cells in transplanted animal eyes. Donor cells in the RCS rat retina survived with only limited proliferation, and hNPCGDNF produced GDNF in vivo. Cell treatment led to significant changes in various pathways related to cell survival, antioxidative stress, phagocytosis, and autophagy. A combined stem cell and trophic factor therapy holds great promise for treating retinal degenerative diseases including retinitis pigmentosa and age-related macular degeneration.<\/jats:p>","DOI":"10.1093\/stcltm\/szad054","type":"journal-article","created":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T07:03:12Z","timestamp":1696316592000},"page":"727-744","source":"Crossref","is-referenced-by-count":11,"title":["Human Neural Progenitors Expressing GDNF Enhance Retinal Protection in a Rodent Model of Retinal Degeneration"],"prefix":"10.1093","volume":"12","author":[{"given":"Saba","family":"Shahin","sequence":"first","affiliation":[{"name":"Board of Governors Regenerative Medicine Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center , Los Angeles, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Tan","sequence":"additional","affiliation":[{"name":"Board of Governors Regenerative Medicine Institute, Department of 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