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Human Neural Progenitors Expressing GDNF Enhance Retinal Protection in a Rodent Model of Retinal Degeneration.
Saba Shahin1, Patrick Tan1, Jason Chetsawang1
1Board of Governors Regenerative Medicine Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Stem Cells Translational Medicine
|October 3, 2023
Summary
Combined stem cell and trophic factor therapy shows promise for retinal degenerative diseases. Engineered human neural progenitor cells (hNPC) expressing GDNF improved visual function and photoreceptor survival in rat models.
Area of Science:
- Ophthalmology
- Regenerative Medicine
- Neuroscience
Background:
- Retinal degenerative diseases lack effective treatments, especially for later stages.
- Current preclinical models often fail to translate to clinical settings due to disease stage differences.
- Inflammation, oxidative stress, and declining trophic support characterize retinal degeneration.
Purpose of the Study:
- To evaluate stem cell therapy using human neural progenitor cells (hNPC) and GDNF-engineered hNPC (hNPCGDNF) in a rat model of retinal degeneration.
- To assess the efficacy of these therapies at both early and later disease stages.
- To investigate the therapeutic mechanisms, including cell survival, neuroprotection, and pathway modulation.
Main Methods:
- Subretinal injection of hNPC and hNPCGDNF into Royal College of Surgeon (RCS) rats at early and late disease stages.
- Assessment of visual function, retinal morphology, and photoreceptor survival.
- Analysis of donor cell survival, GDNF expression, and relevant cellular pathways (e.g., cell survival, oxidative stress, phagocytosis, autophagy).
Main Results:
- hNPCGDNF treatment enhanced visual function more than hNPC alone in early-stage disease.
- Both cell types preserved retinal morphology compared to controls.
- hNPCGDNF provided broader photoreceptor protection than hNPC at both early and late intervention times.
- Donor cells survived in vivo, and hNPCGDNF produced GDNF.
- Significant pathway changes related to cell survival, antioxidative stress, phagocytosis, and autophagy were observed.
Conclusions:
- Stem cell therapy, particularly with GDNF-engineered hNPC, holds significant promise for treating retinal degenerative diseases.
- Therapeutic effects include improved visual function, enhanced photoreceptor survival, and modulation of key cellular pathways.
- Combined stem cell and trophic factor approaches are critical for addressing the complexities of advanced retinal degeneration.
