Current applications and prospects of stem cells in the treatment of corneal diseases

Table 1 Comprehensive applications of stem cells in the corneal field

Stem cell type	Applications in corneal treatment	Advantages	Key safety concerns	Major technical bottlenecks
ESCs	Generate corneal epithelial/stromal/endothelial cells for tissue regeneration, preclinical corneal development/disease modeling	Unlimited self-renewal, high pluripotency and differentiation potential	Ethical controversy, high immunogenicity (allogeneic), teratoma formation (undifferentiated cells)	Optimizing directed differentiation, resolving ethical and regulatory barriers
iPSCs	Differentiate into corneal epithelial/endothelial cells for transplantation, disease modeling and drug testing	Autologous source (no immune rejection), unlimited supply, versatile differentiation potential	Tumorigenicity (residual undifferentiated cells), genetic/epigenetic mutations during reprogramming	Scalable and stable directed differentiation into functional corneal cells, low-cost reprogramming/culture
MSCs	Promote corneal wound healing/epithelial regeneration, reduce LSCD inflammation/neovascularization, corneal scaffold construction for tissue engineering	Immunomodulatory effects, multi-lineage differentiation, readily accessible and expandable, no ethical controversy	Variable paracrine potency by tissue source, TGF-β1/TGF-β3 imbalance risk, incomplete long-term safety data	Standardizing EV isolation and cargo characterization, optimizing preconditioning protocols for desired phenotypes
LSCs	Autologous/allogeneic transplantation for LSCD, CLET and SLET procedures	Native corneal epithelial stem cells, proven clinical efficacy, low immunogenicity (autologous)	Phenotype loss during in vitro culture, low survival rate in damaged ocular microenvironment (allogeneic)	Maintaining stemness in vitro culture, improving transplanted cell survival, developing off-the-shelf allogeneic products
NSCs	Corneal nerve regeneration and pain management, enhance corneal sensitivity and function	Specific differentiation into neural lineages, targeted nerve repair	Low immunogenicity, potential off-target differentiation in ocular microenvironment	Promoting integration with host corneal nerve system, optimizing localized delivery
EPCs	Corneal endothelial regeneration, improve endothelial cell density and corneal transparency	Autologous source, targeted endothelial repair	Low cell yield, poor in vitro expansion ability	Enhancing in vitro expansion efficiency, improving differentiation into functional corneal endothelial cells
ADSCs	Promote corneal wound healing/epithelial regeneration, reduce corneal injury inflammation/scarring	Abundant and readily accessible, autologous transplantation available, multi-lineage differentiation	Low directed differentiation efficiency, potential fat deposition in corneal tissue	Improving directed differentiation into corneal epithelial cells, developing targeted delivery systems
DPSCs	Corneal stromal regeneration, promote stromal cell proliferation and improve corneal transparency	Ethically uncontroversial, autologous source, multi-lineage differentiation	Low stromal differentiation efficiency, potential foreign body reaction	Optimizing stromal differentiation protocols, matching corneal stroma mechanical properties
Skin-derived stem cells	Corneal epithelial regeneration, promote epithelial cell proliferation and restore corneal transparency	Abundant source, easy isolation, autologous transplantation available	Potential epidermal differentiation in ocular surface, immunogenicity (allogeneic)	Improving corneal epithelial directed differentiation, avoiding off-target phenotype
RPE stem cells	Corneal endothelial regeneration, enhance endothelial cell density and maintain corneal hydration	Ethically uncontroversial, autologous source, targeted endothelial repair	Low differentiation efficiency, potential RPE phenotype retention	Optimizing differentiation into corneal endothelial cells, verifying long-term functional stability

ESC: Embryonic stem cell; iPSC: Induced pluripotent stem cell; MSC: Mesenchymal stem cell; LSCD: Limbal stem cell deficiency; TGF: Transforming growth factor; EV: Extracellular vesicle; LSC: Limbal stem cell; CLET: Cultured limbal epithelial transplantation; SLET: Simple limbal epithelial transplantation; NSC: Neural stem cell; EPC: Endothelial progenitor cell; ADSC: Adipose-derived stem cell; DPSC: Dental pulp stem cell; RPE: Retinal pigment epithelium.