• Advancements in Tissue Engineering and Stem Cell Therapy for Optic Nerve Regeneration: The Role of Nfe3
  • Niloofar Niroomand Firoozabad ,1,*
    1. Medical university of Mashhad


  • Introduction: Optic nerve damage, resulting from conditions such as glaucoma or traumatic injuries, leads to irreversible vision loss due to the limited regenerative capacity of retinal ganglion cells (RGCs). Traditional treatments have been largely ineffective in restoring vision, highlighting the need for innovative approaches. Recent advancements in tissue engineering and stem cell therapy offer promising solutions for optic nerve regeneration. This paper explores the potential of Nuclear Factor Erythroid 3 (Nfe3) in promoting the regrowth of optic nerve fibers, presenting a novel avenue for restoring vision in affected individuals. Tissue engineering and stem cell therapy are pivotal strategies in regenerative medicine. Biomaterial scaffolds that mimic the extracellular matrix provide a supportive environment for cells to attach, grow, and differentiate, while releasing growth factors to enhance regeneration. Techniques have been developed to convert stem cells, such as induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), into retinal ganglion cells (RGCs) capable of replacing damaged cells. Additionally, gene therapy can improve the survival and integration of transplanted cells. Tools like CRISPR/Cas9 enable the modification of stem cells to express neuroprotective factors, further enhancing their regenerative potential. Nfe3 is a crucial protein for optic nerve regeneration. Research has shown that stimulating Nfe3 production in adult mice with crushed optic nerves leads to significant regrowth of nerve fibers without adverse effects. Gene therapy techniques that stimulate Nfe3 production have demonstrated successful regeneration of nerve fibers in damaged optic nerves. The effectiveness of Nfe3 in promoting optic nerve regeneration suggests its potential in treating other nerve injuries in the brain and spinal cord, making it a promising target for developing therapies for neurodegenerative diseases and traumatic injuries. Tissue engineering and stem cell therapy are pivotal strategies in regenerative medicine. Biomaterial scaffolds that mimic the extracellular matrix provide a supportive environment for cells to attach, grow, and differentiate, while releasing growth factors to enhance regeneration. Techniques have been developed to convert stem cells, such as induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), into retinal ganglion cells (RGCs) capable of replacing damaged cells. Additionally, gene therapy can improve the survival and integration of transplanted cells. Tools like CRISPR/Cas9 enable the modification of stem cells to express neuroprotective factors, further enhancing their regenerative potential. Nfe3 is a crucial protein for optic nerve regeneration. Research has shown that stimulating Nfe3 production in adult mice with crushed optic nerves leads to significant regrowth of nerve fibers without adverse effects. Gene therapy techniques that stimulate Nfe3 production have demonstrated successful regeneration of nerve fibers in damaged optic nerves. The effectiveness of Nfe3 in promoting optic nerve regeneration suggests its potential in treating other nerve injuries in the brain and spinal cord, making it a promising target for developing therapies for neurodegenerative diseases and traumatic injuries.
  • Methods: Experimental models, particularly rodents, are used to study the effects of Nfe3 on optic nerve regeneration. These models involve inducing optic nerve injury through controlled crush injuries and subsequently administering Nfe3 gene therapy using viral vectors. Biomaterial scaffolds are developed and characterized to support cell growth and differentiation. Pluripotent stem cells (iPSCs and ESCs) are cultured and induced to differentiate into RGCs. Gene editing tools like CRISPR/Cas9 are employed to enhance the expression of neuroprotective factors in stem cells. Delivery of Nfe3 genes to target cells is achieved using viral vectors, such as adeno-associated viruses (AAVs). Quantitative PCR and Western blotting are used to confirm gene expression levels.
  • Results: Significant regrowth of nerve fibers was observed in animal models treated with Nfe3 gene therapy. Histological analysis using immunohistochemistry showed that the regenerated fibers exhibited proper orientation and connectivity with target tissues. The density of regenerating axons was significantly higher in the Nfe3-treated group compared to controls. Behavioral tests, such as the optokinetic response (OKR) and visual cliff test, indicated partial recovery of visual function in treated animals. These tests demonstrated that the regenerated fibers were not only structurally intact but also functionally active. The biomaterial scaffolds were found to be biocompatible, with no signs of chronic inflammation or immune rejection. The gene therapy approach did not result in tumor formation or other adverse effects, as confirmed by long-term monitoring and histopathological analysis. Nfe3 gene therapy showed superior results compared to other regenerative factors, such as BDNF and CNTF, in terms of both nerve regrowth and functional recovery. Statistical analysis using ANOVA and post-hoc tests confirmed the significance of these findings.
  • Conclusion: Combining tissue engineering, stem cell therapy, and the application of Nfe3 represents a significant advancement in optic nerve regeneration. These approaches offer a promising way to restore vision and improve the quality of life for individuals with optic nerve damage. Future research should focus on optimizing these techniques and translating them into clinical therapies. The potential of Nfe3 in treating other forms of nerve injuries in the brain and spinal cord also warrants further investigation.
  • Keywords: Optic nerve regeneration, tissue engineering, stem cell therapy, Nfe3