Abstract
Severe corneal disorders due to infective aetiologies, trauma, chemical injuries, and chronic cicatricial inflammations, are among vision-threatening pathologies leading to permanent corneal scarring. The whole cornea or lamellar corneal transplantation is often used as a last resort to restore vision. However, limited autologous tissue sources and potential adverse post-allotransplantation sequalae urge the need for more robust and strategic alternatives. Contemporary management using cultivated corneal epithelial transplantation has paved the way for utilizing stem cells as a regenerative potential. Humaninduced pluripotent stem cells (hiPSCs) can generate ectodermal progenitors and potentially be used for ocular surface regeneration. This review summarizes the process of corneal morphogenesis and the signaling pathways underlying the development of corneal epithelium, which is key to translating the maturation and differentiation process of hiPSCs in vitro. The current state of knowledge and methodology for driving efficient corneal epithelial cell differentiation from pluripotent stem cells are highlighted.
Graphical Abstract
[http://dx.doi.org/10.1136/bjophthalmol-2018-312292] [PMID: 30409914]
[http://dx.doi.org/10.1016/S2214-109X(17)30393-5] [PMID: 29032195]
[http://dx.doi.org/10.1016/j.brainresbull.2009.05.019]
[http://dx.doi.org/10.1016/j.jtos.2017.11.002] [PMID: 29113917]
[http://dx.doi.org/10.1155/2016/9798374] [PMID: 26788074]
[http://dx.doi.org/10.5966/sctm.2011-0037] [PMID: 23197757]
[http://dx.doi.org/10.1097/ICO.0000000000002136] [PMID: 31517719]
[http://dx.doi.org/10.1016/j.exer.2009.12.010] [PMID: 20036654]
[http://dx.doi.org/10.1136/bjo.81.10.814] [PMID: 9486017]
[http://dx.doi.org/10.1097/ICU.0000000000000378] [PMID: 28399066]
[PMID: 6618809]
[http://dx.doi.org/10.1038/nature07406] [PMID: 18830243]
[http://dx.doi.org/10.4252/wjsc.v7.i2.281] [PMID: 25815115]
[http://dx.doi.org/10.1016/j.ophtha.2008.12.017] [PMID: 19410942]
[http://dx.doi.org/10.1016/j.preteyeres.2021.101011]
[http://dx.doi.org/10.1016/j.ophtha.2014.04.025] [PMID: 24908203]
[http://dx.doi.org/10.1007/3-540-31226-9_2]
[http://dx.doi.org/10.5500/wjt.v4.i2.111] [PMID: 25032100]
[http://dx.doi.org/10.1002/stem.1999] [PMID: 25786664]
[http://dx.doi.org/10.1097/ICO.0000000000002074] [PMID: 31403532]
[http://dx.doi.org/10.1097/ICO.0000000000002358] [PMID: 32639314]
[http://dx.doi.org/10.1097/ICO.0000000000000534] [PMID: 26203759]
[http://dx.doi.org/10.4103/2320-3897.174344]
[http://dx.doi.org/10.1136/bjo.2010.188714] [PMID: 21097786]
[http://dx.doi.org/10.1002/stem.1694] [PMID: 24590515]
[http://dx.doi.org/10.1007/s10792-007-9177-z] [PMID: 18084724]
[http://dx.doi.org/10.1177/0310057X1804600204] [PMID: 29519218]
[http://dx.doi.org/10.3390/jcm9113696] [PMID: 33217910]
[http://dx.doi.org/10.1016/j.joco.2018.04.001] [PMID: 30555963]
[http://dx.doi.org/10.1038/eye.2008.305] [PMID: 18949010]
[http://dx.doi.org/10.1186/s40662-018-0122-1] [PMID: 30410944]
[http://dx.doi.org/10.3389/fimmu.2018.02666] [PMID: 30515159]
[http://dx.doi.org/10.3390/jcm6120115] [PMID: 29206194]
[http://dx.doi.org/10.1016/j.survophthal.2017.02.002] [PMID: 28232219]
[PMID: 31523119]
[http://dx.doi.org/10.3390/jcm10020317] [PMID: 33467167]
[http://dx.doi.org/10.1159/000492838] [PMID: 30134223]
[http://dx.doi.org/10.21037/sci.2018.04.02] [PMID: 30050918]
[http://dx.doi.org/10.1111/jcmm.16851] [PMID: 34390186]
[http://dx.doi.org/10.1016/j.cell.2006.07.024] [PMID: 16904174]
[http://dx.doi.org/10.1038/s12276-020-0383-3] [PMID: 32080339]
[http://dx.doi.org/10.1186/s13287-018-0876-3] [PMID: 29751774]
[http://dx.doi.org/10.1159/000429697]
[http://dx.doi.org/10.1016/B978-1-4832-3090-0.50007-1]
[http://dx.doi.org/10.1167/iovs.05-0818] [PMID: 16303940]
[http://dx.doi.org/10.1007/s00441-002-0693-x] [PMID: 12715147]
[http://dx.doi.org/10.1016/S1542-0124(12)70102-7] [PMID: 18264652]
[http://dx.doi.org/10.4161/org.4.2.5850] [PMID: 19122781]
[http://dx.doi.org/10.3389/fnins.2018.00087] [PMID: 29515359]
[http://dx.doi.org/10.3389/fcell.2020.595896] [PMID: 33425902]
[http://dx.doi.org/10.1242/dev.128.11.2019] [PMID: 11493524]
[http://dx.doi.org/10.1242/dev.00723] [PMID: 12944429]
[http://dx.doi.org/10.1242/dev.129.17.4057] [PMID: 12163408]
[http://dx.doi.org/10.1016/j.ydbio.2012.04.023] [PMID: 22561201]
[http://dx.doi.org/10.1186/s12886-022-02256-7] [PMID: 35034608]
[http://dx.doi.org/10.3389/fgene.2018.00479] [PMID: 30386378]
[http://dx.doi.org/10.1203/01.PDR.0000096455.00657.98] [PMID: 14561779]
[http://dx.doi.org/10.1016/j.ydbio.2016.05.021] [PMID: 27212025]
[http://dx.doi.org/10.1242/dev.041202] [PMID: 19906857]
[http://dx.doi.org/10.1242/dev.121.10.3267] [PMID: 7588061]
[http://dx.doi.org/10.1242/dev.107953] [PMID: 25406393]
[http://dx.doi.org/10.1016/j.ydbio.2011.04.023] [PMID: 21539829]
[http://dx.doi.org/10.1155/2013/103947] [PMID: 23533700]
[http://dx.doi.org/10.1006/exer.1998.0593] [PMID: 10079137]
[http://dx.doi.org/10.1074/jbc.M113.504399] [PMID: 24142692]
[http://dx.doi.org/10.1074/jbc.M117.793117] [PMID: 28916725]
[http://dx.doi.org/10.1167/iovs.03-0449] [PMID: 14744882]
[http://dx.doi.org/10.1167/iovs.17-21826] [PMID: 28549095]
[http://dx.doi.org/10.1016/j.ydbio.2011.05.005] [PMID: 21600198]
[http://dx.doi.org/10.1016/j.stem.2008.09.003] [PMID: 18983969]
[http://dx.doi.org/10.1007/s00439-019-02052-2] [PMID: 31359131]
[http://dx.doi.org/10.1002/dvdy.22033]
[http://dx.doi.org/10.3389/fmed.2020.00043] [PMID: 32133365]
[http://dx.doi.org/10.1167/iovs.16-21217] [PMID: 28253399]
[http://dx.doi.org/10.1101/cshperspect.a022194]
[http://dx.doi.org/10.1006/dbio.2001.0480] [PMID: 11784073]
[PMID: 26015770]
[http://dx.doi.org/10.1186/jbiol29] [PMID: 16403239]
[http://dx.doi.org/10.1007/s12551-009-0011-x] [PMID: 28509987]
[http://dx.doi.org/10.1074/jbc.RA118.005527] [PMID: 30552118]
[http://dx.doi.org/10.1371/journal.pone.0117581]
[http://dx.doi.org/10.1242/dmm.025262] [PMID: 27483349]
[http://dx.doi.org/10.1167/iovs.15-18103] [PMID: 26968737]
[http://dx.doi.org/10.1002/(SICI)1526-968X(200001)26:1<15:AID-GENE5>3.0.CO;2-V] [PMID: 10660670]
[PMID: 21850167]
[PMID: 11053261]
[http://dx.doi.org/10.1038/emboj.2008.196] [PMID: 18818691]
[http://dx.doi.org/10.1371/journal.pone.0117089] [PMID: 25615698]
[PMID: 10711683]
[PMID: 7689546]
[http://dx.doi.org/10.1016/j.copbio.2019.05.011] [PMID: 31386977]
[http://dx.doi.org/10.1038/s41536-020-00100-4] [PMID: 33200672]
[http://dx.doi.org/10.1371/journal.pone.0212369] [PMID: 30865653]
[http://dx.doi.org/10.1038/nbt.4114] [PMID: 29553577]
[http://dx.doi.org/10.1016/j.stemcr.2014.03.011] [PMID: 24936453]
[http://dx.doi.org/10.3390/cells10112951] [PMID: 34831174]
[http://dx.doi.org/10.1155/2016/8304879] [PMID: 27293447]
[http://dx.doi.org/10.2217/rme-2016-0054]
[http://dx.doi.org/10.1016/j.stemcr.2015.08.015] [PMID: 26411904]
[http://dx.doi.org/10.1007/s40259-021-00503-9] [PMID: 34727354]
[http://dx.doi.org/10.3791/58279] [PMID: 30417867]
[http://dx.doi.org/10.1371/journal.pone.0183303] [PMID: 28813511]
[http://dx.doi.org/10.1167/iovs.10-6486] [PMID: 21357396]
[http://dx.doi.org/10.1098/rsob.120167] [PMID: 23576785]
[http://dx.doi.org/10.1016/j.scr.2020.101868] [PMID: 32603880]
[http://dx.doi.org/10.1002/cbin.10484] [PMID: 25939663]
[http://dx.doi.org/10.1007/s00441-018-2934-7.Basement]
[http://dx.doi.org/10.1016/j.celrep.2018.10.032] [PMID: 30404017]
[PMID: 20664695]
[http://dx.doi.org/10.1186/s13287-019-1354-2] [PMID: 31383008]
[http://dx.doi.org/10.1002/cbic.201000032] [PMID: 20183843]
[http://dx.doi.org/10.1016/j.biomaterials.2014.10.055] [PMID: 25477171]
[http://dx.doi.org/10.1016/j.tips.2009.10.002] [PMID: 19896224]
[http://dx.doi.org/10.1002/stem.2750] [PMID: 29226476]
[http://dx.doi.org/10.1242/dev.127.20.4325] [PMID: 11003833]
[http://dx.doi.org/10.1016/j.stemcr.2013.12.014] [PMID: 24527395]
[http://dx.doi.org/10.1186/s13287-017-0738-4] [PMID: 29284513]
[http://dx.doi.org/10.1242/dev.125393] [PMID: 26443636]
[http://dx.doi.org/10.1093/jmcb/mjv030] [PMID: 25990320]
[http://dx.doi.org/10.1371/journal.pone.0045435] [PMID: 23029008]
[http://dx.doi.org/10.1002/stem.1068] [PMID: 22367714]
[http://dx.doi.org/10.1038/cr.2008.302] [PMID: 19002158]
[http://dx.doi.org/10.5966/sctm.2012-0156] [PMID: 23981725]
[http://dx.doi.org/10.1038/s41598-017-02824-8] [PMID: 28588247]
[http://dx.doi.org/10.1007/s00405-014-3237-6] [PMID: 25138153]
[http://dx.doi.org/10.1016/j.transproceed.2017.09.047] [PMID: 29198663]
[http://dx.doi.org/10.1007/s13765-018-0400-6]
[http://dx.doi.org/10.1007/s12015-011-9278-y] [PMID: 21655946]
[http://dx.doi.org/10.1098/rstb.2017.0230] [PMID: 29786564]
[http://dx.doi.org/10.1167/iovs.04-0044] [PMID: 15557438]
[http://dx.doi.org/10.1634/stemcells.2006-0516] [PMID: 17255521]
[http://dx.doi.org/10.1371/journal.pone.0013192] [PMID: 20949137]
[http://dx.doi.org/10.3969/j.issn.1672-5123.2009.05.003]
[http://dx.doi.org/10.1155/2017/7678637] [PMID: 29230251]
[http://dx.doi.org/10.1007/s12015-021-10262-3] [PMID: 34532844]
[http://dx.doi.org/10.3390/cimb43030147] [PMID: 34940121]
[http://dx.doi.org/10.1038/nprot.2017.007] [PMID: 28253236]
[http://dx.doi.org/10.1038/s41598-020-69020-z] [PMID: 32709896]