Novel developments in retinal regeneration: Advances and future outlooks in stem cell therapy

Table 1 Gene editing and retinal organoid strategies in retinal therapy

Strategy	Application	Current limitations	Ref.
CRISPR/Cas9 gene editing	Correction of pathogenic mutations in patient-specific iPSCs	Off-target effects, ethical concerns, and delivery efficiency	[26,27,30,31]
Retinal organoids	Modeling retinal development and disease; source of transplantable cells	Limited maturation, variability, and scalability for clinical use	[29-42]

iPSCs: Induced pluripotent stem cells.

Table 2 Key differences between human embryonic stem cell- and induced pluripotent stem cell-based retinal therapies

	hESC-based therapies	iPSC-based therapies
Ethical considerations	Derived from human embryos; subject to ethical and regulatory scrutiny in many jurisdictions	Generated from adult somatic cells (e.g., fibroblasts, blood cells); avoids embryo use and associated ethical controversy
Immune compatibility	Typically allogeneic; requires systemic immunosuppression or HLA matching to prevent rejection	Autologous options reduce rejection risk; potential for patient-specific therapy; hypoimmunogenic engineered iPSC lines under development
Genomic stability	Established lines with relatively stable karyotype after differentiation	Risk of genomic and epigenetic instability during reprogramming and passaging; batch-to-batch variability
Tumorigenicity risk	Residual undifferentiated cells pose risk but can be mitigated with stringent quality control	Similar risk plus concerns related to incomplete reprogramming and epigenetic memory
Manufacturing cost and timeline	Scalable, standardized production; cost per dose potentially lower when scaled	Personalized autologous production is expensive and timeconsuming; emerging universal donor iPSC banks may mitigate costs

hESC: Human embryonic stem cell; iPSC: Induced pluripotent stem cell.