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

Not specific in corneal endothelium

Sphere-forming assay

Nestin, GFAP, β3-tubulin, αSMA

Dissociated sphere cells showed hexagonal shape and pumping activity; no p75^NTR 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

P75^NTR, 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, p75^NTR, 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, p75^NTR, 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, p75^NTR, 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]