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Table 1 Summary of studies reporting human corneal endothelial progenitors with potential location, identification, and differentiated functions

From: Regenerative capacity of the corneal transition zone for endothelial cell therapy

Possible location of endothelial progenitors Methods of identification Markers Remarks References
Not specific in corneal endothelium Sphere-forming assay Nestin, GFAP, β3-tubulin, αSMA Dissociated sphere cells showed hexagonal shape and pumping activity; no p75NTR expression. [45]
Peripheral endothelium BrdU labeling and immunostaining Alkaline phosphatase, telomerase Progenitors in a niche at the junction between corneal endothelium and TM. [49]
TM and transition zone between TM and corneal periphery Corneal wounding model and immunostaining Alkaline phosphatase, nestin, telomerase, Oct3/4, Pax6, Wnt1, Sox2 Wounding activated Oct3/4 and Wnt1 expression as a response to initiate the endothelial repair process. [50]
Peripheral endothelium Sphere-forming assay Nil PE had a significantly higher percentage of sphere formation, representing precursor density. [51]
Peripheral endothelium Immunostaining and flow cytometry Lgr5, Hedgehog pathway markers (SHH, Gli1, Gli2) Lgr5+ cells were proliferative. Generation of differentiated corneal endothelium and functional assay was not demonstrated. [52]
Central and peripheral endothelium; progenitor enriched at transition region between CE and TM Immunostaining and flow cytometry P75NTR, Sox9, FoxC2 Expressed partial properties of neural crest and periocular mesenchyme; differentiated cell sheet had pumping activity by Ussing chamber system and in vivo transplantation to rabbit corneas. [53]
Whole corneal endothelium of normal and FECD corneas Colony-forming populations; > 80 passages Pax3, nestin, Sox9, AP-2β, p75NTR, Sox2, Lgr5, p63, Oct4 Adult corneal endothelium harbored neural crest-derived progenitors capable of perpetual proliferation and formation of endothelial layer exhibiting trans-endothelial resistance. [54]
Trabecular meshwork 3D Matrigel culture to activate BMP signaling AQP1, MGP, CHI3L1, AnkG, Oct4, Sox2, Nanog, ABCG2, p75NTR, FOXD3, Sox9, Sox10, MSX1 TM progenitors were multipotent to differentiate into corneal endothelial cells, adipocytes, and chondrocytes. [55]
Transition zone (inner TZ) Immunostaining, cell culture Lgr5, telomerase, nestin, Sox2, p75NTR, Pitx2, HNK1 Inner TZ, adjacent to PE, contained progenitors that projected as multicellular clusters into PE. Porcine TZ progenitors differentiated to endothelial monolayer expressing ZO1 and Na+K+ATPase. [56]