11,604
Views
58
CrossRef citations to date
0
Altmetric
Anterior Segment

Corneal Stromal Regeneration: Current Status and Future Therapeutic Potential

ORCID Icon
Pages 278-290 | Received 31 Jul 2019, Accepted 29 Aug 2019, Published online: 20 Sep 2019

References

  • Pellegrini G, Ardigò D, Milazzo G, Iotti G, Guatelli P, Pelosi D, De Luca M. Navigating market authorization: the path holoclar took to become the first stem cell product approved in the European Union. Stem Cells Transl Med. 2018;7(1):146–54. doi:10.1002/sctm.17-0003.
  • Kinoshita S, Koizumi N, Ueno M, Okumura N, Imai K, Tanaka H, Yamamoto Y, Nakamura T, Inatomi T, Bush J, et al. Injection of cultured cells with a ROCK inhibitor for bullous keratopathy. N Engl J Med. 2018 Mar 15;378(11):995–1003. doi:10.1056/NEJMoa1712770.
  • Whitcher JP, Srinivasan M, Upadhyay MP. Corneal blindness: a global perspective. Bull World Health Organ. 2001;79:214–21.
  • Zerbe BL, Belin MW, Ciolino JB. Boston type 1 keratoprosthesis study group. Results from the multicenter Boston type 1 keratoprosthesis study. Ophthalmology. 2006 Oct 1;113(10):1779–84. doi:10.1016/j.ophtha.2006.05.015.
  • Liu C, Paul B, Tandon R, Lee E, Fong K, Mavrikakis I, Herold J, Thorp S, Brittain P, Francis I, et al. The osteo-odonto-keratoprosthesis (OOKP). Seminars in ophthalmology. 2005;20(2):113–28.
  • Tervo T, Vannas A, Tervo K, Holden BA. Histochemical evidence of limited reinnervation of human corneal grafts. Acta Ophthalmol (Copenh). 1985;63(2):207–14. doi:10.1111/j.1755-3768.1985.tb01535.x.
  • Niederer RL, Perumal D, Sherwin T, McGhee CN. Corneal innervation and cellular changes after corneal transplantation: an in vivo confocal microscopy study. Invest Ophthalmol Vis Sci. 2007;48(2):621–26. doi:10.1167/iovs.06-0538.
  • Al-Aqaba MA, Otri AM, Fares U, Miri A, Dua HS. Organization of the regenerated nerves in human corneal grafts. Am J Ophthalmol. 2012;153(1):29–37. doi:10.1016/j.ajo.2011.06.006.
  • Nubile M, Carpineto P, Lanzini M, Calienno R, Agnifili L, Ciancaglini M, Mastropasqua L. Femtosecond laser arcuate keratotomy for the correction of high astigmatism after keratoplasty. Ophthalmology. 2009;116(6):1083–92. doi:10.1016/j.ophtha.2009.01.013.
  • Khodadoust AA, Silverstein AM. Transplantation and rejection of individual cell layers of the cornea. Invest Ophthalmol Vis Sci. 1969;8:180–95.
  • Oliva MS, Schottman T, Gulati M. Turning the tide of corneal blindness. Indian J Ophthalmol. 2012;60(5):423. doi:10.4103/0301-4738.100540.
  • Gain P, Jullienne R, He Z, Aldossary M, Acquart S, Cognasse F, Thuret G. Global survey of corneal transplantation and eye banking. JAMA Ophthalmol. 2016;134(2):167–73. doi:10.1001/jamaophthalmol.2015.4776.
  • Komai Y, Ushiki T. The three-dimensional organization of collagen fibrils in the human cornea and sclera. Invest Ophthalmol Vis Sci. 1991;32:2244–58.
  • Lagali N, Germundsson J, Fagerholm P. The role of Bowman’s layer in corneal regeneration after phototherapeutic keratectomy: a prospective study using in vivo confocal microscopy. Invest Ophthalmol Vis Sci. 2009;50(9):4192–98. doi:10.1167/iovs.09-3781.
  • Bron AJ. The architecture of the corneal stroma. Br J Ophthalmol. 2001;85:379–81. doi:10.1136/bjo.85.4.379.
  • West-Mays JA, Dwivedi DJ. The keratocyte: corneal stromal cell with variable repair phenotypes. Int J Biochem Cell Biol. 2006;38(10):1625–31. doi:10.1016/j.biocel.2006.03.010.
  • Paik DC, Trokel SL, Suh LH. Just what do we know about corneal collagen turnover? Cornea. 2018;37(11):e49–50. doi:10.1097/ICO.0000000000001685.
  • Wilson SL, El Haj AJ, Yang Y. Control of scar tissue formation in the cornea: strategies in clinical and corneal tissue engineering. J Funct Biomater. 2012;3(3):642–87. doi:10.3390/jfb3030642.
  • Michelacci YM. Collagens and proteoglycans of the corneal extracellular matrix. Braz J Med Biol Res. 2003;36(8):1037–46. doi:10.1590/s0100-879x2003000800009.
  • Marfurt CF, Cox J, Deek S, Dvorscak L. Anatomy of the human corneal innervation. Exp Eye Res. 2010;90(4):478–92. doi:10.1016/j.exer.2009.12.010.
  • Belmonte C, Acosta MC, Gallar J. Neural basis of sensation in intact and injured corneas. Exp Eye Res. 2004;78(3):513–25. doi:10.1016/j.exer.2003.09.023.
  • Müller LJ, Marfurt CF, Kruse F, Tervo TM. Corneal nerves: structure, contents and function. Exp Eye Res. 2003;76(5):521–42. doi:10.1016/s0014-4835(03)00050-2.
  • Patel DV, McGhee CN. In vivo laser scanning confocal microscopy confirms that the human corneal sub-basal nerve plexus is a highly dynamic structure. Invest Ophthalmol Vis Sci. 2008;49(8):3409–12. doi:10.1167/iovs.08-1951.
  • Lagali N, Peebo BB, Germundsson J, Edén U, Danyali R, Rinaldo M, Fagerholm P. Laser-scanning in vivo confocal microscopy of the cornea: imaging and analysis methods for preclinical and clinical applications. In: Lagali N, editor. Confocal laser microscopy principles and applications in medicine, biology, and the food sciences. Rijeka (Croatia): InTech; 2013. p. 51–80.
  • Ivarsen A, Asp S, Hjortdal J. Safety and complications of more than 1500 small-incision lenticule extraction procedures. Ophthalmology. 2014;121(4):822–28. doi:10.1016/j.ophtha.2013.11.006.
  • Larkin H. Hyperopia innovations: adding donor stroma is new frontier for hyperopia, presbyopia, keratoconus treatment. Posted: Monday; 2019 Apr 1. Eurotimes. https://www.eurotimes.org/hyperopia-innovations/.
  • Ganesh S, Brar S, Rao PA. Cryopreservation of extracted corneal lenticules after small incision lenticule extraction for potential use in human subjects. Cornea. 2014;33(12):1355–62. doi:10.1097/ICO.0000000000000276.
  • Bhandari V, Ganesh S, Brar S, Pandey R. Application of the SMILE-derived glued lenticule patch graft in microperforations and partial-thickness corneal defects. Cornea. 2016;35(3):408–12. doi:10.1097/ICO.0000000000000741.
  • Wu F, Jin X, Xu Y, Yang Y. Treatment of corneal perforation with lenticules from small incision lenticule extraction surgery: a preliminary study of 6 patients. Cornea. 2015;34(6):658–63. doi:10.1097/ICO.0000000000000397.
  • Ganesh S, Brar S. Femtosecond intrastromal lenticular implantation combined with accelerated collagen cross-linking for the treatment of keratoconus–initial clinical result in 6 eyes. Cornea. 2015;34(10):1331–39. doi:10.1097/ICO.0000000000000539.
  • Yam GH, Yusoff NZ, Goh TW, Setiawan M, Lee XW, Liu YC, Mehta JS. Decellularization of human stromal refractive lenticules for corneal tissue engineering. Sci Rep. 2016 May 23;6:26339. doi:10.1038/srep26339.
  • Liu YC, Teo EPW, Ang HP, Seah XY, Lwin NC, Yam GHF, Mehta JS. Biological corneal inlay for presbyopia derived from small incision lenticule extraction (SMILE). Sci Rep. 2018;8(1):1831. doi:10.1038/s41598-018-20267-7.
  • Lee W, Miyagawa Y, Long C, Cooper DK, Hara H. A comparison of three methods of decellularization of pig corneas to reduce immunogenicity. Int J Ophthalmol. 2014;7:587–93.
  • Yoeruek E, Bayyoud T, Maurus C, Hofmann J, Spitzer MS, Bartz-Schmidt K-U, Szurman P. Decellularization of porcine corneas and repopulation with human corneal cells for tissue-engineered xenografts. Acta Ophthalmol. 2012;90:e125–e131. doi:10.1111/j.1755-3768.2011.02261.x.
  • Ma XY, Zhang Y, Zhu D, Lu Y, Zhou G, Liu W, Cao Y, Zhang WJ. Corneal stroma regeneration with acellular corneal stroma sheets and keratocytes in a rabbit model. PLoS One. 2015;10(7):e0132705. doi:10.1371/journal.pone.0132705.
  • Gonzalez‐Andrades M, de la Cruz Cardona J, Ionescu AM, Campos A, Del Mar Perez M, Alaminos M. Generation of bioengineered corneas with decellularized xenografts and human keratocytes. Invest Ophthalmol Vis Sci. 2011;52:215–22. doi:10.1167/iovs.09-4773.
  • Mirazul Islam M, Sharifi R, Mamodaly S, Islam R, Nahra D, Abusamra DB, Chuen Hui P, Adibnia Y, Goulamaly M, Paschalis EI, et al. Effects of gamma radiation sterilization on the structural and biological properties of decellularized corneal xenografts. Acta Biomater. 2019;96:330–344. doi: 10.1016/j.actbio.2019.07.002.
  • Du L, Wu X. Development and characterization of a full-thickness acellular porcine cornea matrix for tissue engineering. Artif Organs. 2011;35:691–705. doi:10.1111/j.1525-1594.2010.01174.x.
  • Zhang MC, Liu X, Jin Y, Jiang DL, Wei XS, Xie HT. Lamellar keratoplasty treatment of fungal corneal ulcers with acellular porcine corneal stroma. Am J Transplant. 2015;15(4):1068–75. doi:10.1111/ajt.13096.
  • Zheng J, Huang X, Zhang Y, Wang Y, Qin Q, Lin L, Jin X, Lam C, Zhang J. Short-term results of acellular porcine corneal stroma keratoplasty for herpes simplex keratitis. Xenotransplantation. 2019;26(4):e12509. doi: 10.1111/xen.12509.
  • ClinicalTrials.gov identifier: NCT03105466. https://clinicaltrials.gov/ct2/show/NCT03105466
  • Zhang C, Du L, Sun P, Shen L, Zhu J, Pang K, Wu X. Construction of tissue-engineered full-thickness cornea substitute using limbal epithelial cell-like and corneal endothelial cell-like cells derived from human embryonic stem cells. Biomaterials. 2017;124:180–94. doi:10.1016/j.biomaterials.2017.02.003.
  • Zhang K, Ren XX, Li P, Pang KP, Wang H. Construction of a full-thickness human corneal substitute from anterior acellular porcine corneal matrix and human corneal cells. Int J Ophthalmol. 2019;12(3):351–62. doi:10.18240/ijo.2019.03.01.
  • van Essen TH, Lin CC, Hussain AK, Maas S, Lai JL, Linnartz H, van Den Berg TJTP, Salvatori DCF, Luyten GPM, Jager MJ. A fish scale-derived collagen matrix as artificial cornea in rats: properties and potential. Invest Ophthalmol Vis Sci. 2013;54:3224–33. doi:10.1167/iovs.13-11799.
  • Lin CC, Ritch R, Lin SM, Ni MH, Chang YC, Lu YL, Lai HJ, Lin FH. A new fish scale-derived scaffold for corneal regeneration. Eur Cell Mater. 2010;19:50–57.
  • Van Essen TH, Van Zijl L, Possemiers T, Mulder AA, Zwart SJ, Chou CH, Lin CC, Lai HJ, Luyten GP, Tassignon MJ, et al. Biocompatibility of a fish scale-derived artificial cornea: cytotoxicity, cellular adhesion and phenotype, and in vivo immunogenicity. Biomaterials. 2016;81:36–45. doi:10.1016/j.biomaterials.2015.11.015.
  • Chen SC, Telinius N, Lin HT, Huang MC, Lin CC, Chou CH, Hjortdal J. Use of fish scale-derived BioCornea to seal full-thickness corneal perforations in pig models. PLoS One. 2015;10(11):e0143511. doi:10.1371/journal.pone.0143511.
  • Liu Y, Gan L, Carlsson DJ, Fagerholm P, Lagali N, Watsky MA, Munger R, Hodge WG, Priest D, Griffith M. A simple, cross-linked collagen tissue substitute for corneal implantation. Invest Ophthalmol Vis Sci. 2006;47(5):1869–75. doi:10.1167/iovs.05-1339.
  • Fagerholm P, Lagali NS, Carlsson DJ, Merrett K, Griffith M. Corneal regeneration following implantation of a biomimetic tissue‐engineered substitute. Clin Transl Sci. 2009;2(2):162–64. doi:10.1111/j.1752-8062.2008.00083.x.
  • Fagerholm P, Lagali NS, Merrett K, Jackson WB, Munger R, Liu Y, Polarek JW, Söderqvist M, Griffith M. A biosynthetic alternative to human donor tissue for inducing corneal regeneration: 24-month follow-up of a phase 1 clinical study. Sci Transl Med. 2010;2(46):46ra61. doi:10.1126/scitranslmed.3001022.
  • Fagerholm P, Lagali NS, Ong JA, Merrett K, Jackson WB, Polarek JW, Suuronen EJ, Liu Y, Brunette I, Griffith M. Stable corneal regeneration four years after implantation of a cell-free recombinant human collagen scaffold. Biomaterials. 2014;35(8):2420–27. doi:10.1016/j.biomaterials.2013.11.079.
  • Koulikovska M, Rafat M, Petrovski G, Veréb Z, Akhtar S, Fagerholm P, Lagali N. Enhanced regeneration of corneal tissue via a bioengineered collagen construct implanted by a nondisruptive surgical technique. Tissue Eng Part A. 2015;21(5–6):1116–30. doi:10.1089/ten.TEA.2014.0562.
  • Rafat M, Xeroudaki M, Koulikovska M, Sherrell P, Groth F, Fagerholm P, Lagali N. Composite core-and-skirt collagen hydrogels with differential degradation for corneal therapeutic applications. Biomaterials. 2016;83:142–55. doi:10.1016/j.biomaterials.2016.01.004.
  • Lagali NS, Xeroudaki M, Thangavelu M, Fagerholm P, Mukwaya A, Lennikov A, Rafat M. Double-crosslinked bioengineered collagen implants for corneal stromal transplantation: evaluation in a porcine model. ARVO annual meeting abstract 2018. Invest Ophthalmol Vis Sci. 2018;59(9):2251. doi:10.1167/iovs.17-23678.
  • Drechsler CC, Kunze A, Kureshi A, Grobe G, Reichl S, Geerling G, Daniels JT, Schrader S. Development of a conjunctival tissue substitute on the basis of plastic compressed collagen. J Tissue Eng Regen Med. 2017;11:896–904. doi:10.1002/term.1991.
  • Schrader S, Witt J, Geerling G. Plastic compressed collagen transplantation–a new option for corneal surface reconstruction? Acta Ophthalmol (Copenh). 2018 Sep 1;96:6. doi:10.1111/aos.13801.
  • González-Andrades M, Mata R, González-Gallardo MDC, Medialdea S, Arias-Santiago S, Martínez-Atienza J, Ruiz-García A, Pérez-Fajardo L, Lizana-Moreno A, Garzón I, et al. A study protocol for a multicentre randomised clinical trial evaluating the safety and feasibility of a bioengineered human allogeneic nanostructured anterior cornea in patients with advanced corneal trophic ulcers refractory to conventional treatment. BMJ Open. 2017;7(9):e016487. doi:10.1136/bmjopen-2017-016487.
  • Andrades MG, Martinez-Atienza J, Campos A, Arias-Santiago S, Gallardo CG, Mataix B, Medialdea S, Ruiz-Garcia A, Mata R, Cuende N, et al. Preliminary results of a multicenter randomized clinical trial evaluating the safety and feasibility of an allogeneic nanostructured artificial anterior human cornea. Cytotherapy. 2017;19(5):S26. doi:10.1016/j.jcyt.2017.02.052.
  • ClinicalTrials.gov identifier: NCT01765244. https://clinicaltrials.gov/ct2/show/NCT01765244
  • Gonzalez Andrades M, González Gallardo MC, Mataix B, Medialdea S, Martinez-Atienza J, Ruiz-Garcia A, Arias S, Campos A, Mata R, Cuende N, et al. Results of a Phase I-IIA multicentre clinical trial evaluating an allogeneic nanostructured artificial anterior human cornea. Oral session presented at: association for Research in Vision and Ophthalmology Annual Meeting; 2019; Vancouver (Canada); Abstract Number: 2231.
  • Sani ES, Kheirkhah A, Rana D, Sun Z, Foulsham W, Sheikhi A, Khademhosseini A, Dana R, Annabi N. Sutureless repair of corneal injuries using naturally derived bioadhesive hydrogels. Sci Adv. 2019;5(3):eaav1281. doi:10.1126/sciadv.aav1281.
  • Assmann A, Vegh A, Ghasemi-Rad M, Bagherifard S, Cheng G, Sani ES, Ruiz-Esparza GU, Noshadi I, Lassaletta AD, Gangadharan S, et al. A highly adhesive and naturally derived sealant. Biomaterials. 2017;140:115–27. doi:10.1016/j.biomaterials.2017.06.004.
  • Isaacson A, Swioklo S, Connon CJ. 3D bioprinting of a corneal stroma equivalent. Exp Eye Res. 2018;173:188–93. doi:10.1016/j.exer.2018.05.010.
  • Sorkio A, Koch L, Koivusalo L, Deiwick A, Miettinen S, Chichkov B, Skottman H. Human stem cell based corneal tissue mimicking structures using laser-assisted 3D bioprinting and functional bioinks. Biomaterials. 2018;171:57–71. doi:10.1016/j.biomaterials.2018.04.034.
  • Basu S, Hertsenberg AJ, Funderburgh ML, Burrow MK, Mann MM, Du Y, Du Y, Lathrop KL, Syed-Picard FN, Adams SM, et al. Human limbal biopsy-derived stromal stem cells prevent corneal scarring. Sci Transl Med. 2014;6(266):266ra172. doi:10.1126/scitranslmed.3009644.
  • ClinicalTrials.gov identifier: NCT02948023. https://clinicaltrials.gov/ct2/show/NCT02948023
  • ClinicalTrials.gov identifier: NCT03295292, https://clinicaltrials.gov/ct2/show/NCT03295292
  • Du Y, Carlson EC, Funderburgh ML, Birk DE, Pearlman E, Guo N, Kao WW-Y, Funderburgh JL. Stem cell therapy restores transparency to defective murine corneas. Stem Cells. 2009;27:1635–42. doi:10.1002/stem.v27:7.
  • Wu J, Du Y, Watkins SC, Funderburgh JL, Wagner WR. The engineering of organized human corneal tissue through the spatial guidance of corneal stromal stem cells. Biomaterials. 2012;33:1343–52. doi:10.1016/j.biomaterials.2011.10.068.
  • Polisetty N, Fatima A, Madhira SL, Sangwan VS, Vemuganti GK. Mesenchymal cells from limbal stroma of human eye. Mol Vis. 2008;14:431–42.
  • Alió JL, Del Barrio JL, El Zarif M, Azaar A, Makdissy N, Khalil C, Harb W, El Achkar I, Jawad ZA, De Miguel MP. Regenerative surgery of the corneal stroma for advanced keratoconus: 1-year outcomes. Am J Ophthalmol. 2019;203:53–68. doi:10.1016/j.ajo.2019.02.009.
  • Shojaati G, Khandaker I, Funderburgh ML, Mann MM, Basu R, Stolz DB, Geary ML, Dos Santos A, Deng SX, Funderburgh JL. Mesenchymal stem cells reduce corneal fibrosis and inflammation via extracellular vesicle-mediated delivery of miRNA. Stem Cells Transl Med. Jul 10 2019. doi: 10.1002/sctm.18-0297
  • Hayashi R, Ishikawa Y, Sasamoto Y, Katori R, Nomura N, Ichikawa T, Araki S, Soma T, Kawasaki S, Sekiguchi K, et al. Co-ordinated ocular development from human iPS cells and recovery of corneal function. Nature. 2016;531(7594):376. doi:10.1038/nature17000.
  • Foster JW, Wahlin K, Adams SM, Birk DE, Zack DJ, Chakravarti S. Cornea organoids from human induced pluripotent stem cells. Sci Rep. 2017;7:41286. doi:10.1038/srep41286.
  • Del Barrio JL, Chiesa M, Garagorri N, Garcia-Urquia N, Fernandez-Delgado J, Bataille L, Rodriguez A, Arnalich-Montiel F, Zarnowski T, de Toledo JP, et al. Acellular human corneal matrix sheets seeded with human adipose-derived mesenchymal stem cells integrate functionally in an experimental animal model. Exp Rye Res. 2015;132:91–100. doi:10.1016/j.exer.2015.01.020.
  • Shojaati G, Khandaker I, Sylakowski K, Funderburgh ML, Du Y, Funderburgh JL. Compressed collagen enhances stem cell therapy for corneal scarring. Stem Cells Transl Med. 2018;7(6):487–94. doi:10.1002/sctm.17-0258.
  • Liu H, Zhang J, Liu CY, Hayashi Y, Kao WW. Bone marrow mesenchymal stem cells can differentiate and assume corneal keratocyte phenotype. J Cell Mol Med. 2012;16:1114–24. doi:10.1111/j.1582-4934.2011.01306.x.
  • Arnalich‐Montiel F, Pastor S, Blazquez‐Martinez A, Fernandez‐Delgado J, Nistal M, Alio JL, De Miguel MP. Adipose‐derived stem cells are a source for cell therapy of the corneal stroma. Stem Cells. 2008 Feb;26(2):570–79. doi:10.1634/stemcells.2007-0653.
  • Liu H, Zhang J, Liu CY, Wang IJ, Sieber M, Chang J, Jester JV, Kao WW. Cell therapy of congenital corneal diseases with umbilical mesenchymal stem cells: lumican null mice. PLoS One. 2010;5(5):e10707. doi:10.1371/journal.pone.0010707.
  • Coulson-Thomas VJ, Caterson B, Kao WW. Transplantation of human umbilical mesenchymal stem cells cures the corneal defects of mucopolysaccharidosis VII mice. Stem Cells. 2013;31(10):2116–26. doi:10.1002/stem.1481.
  • Yun YI, Park SY, Lee HJ, Ko JH, Kim MK, Wee WR, Reger RL, Gregory CA, Choi H, Fulcher SF, et al. Comparison of the anti-inflammatory effects of induced pluripotent stem cell-derived and bone marrow-derived mesenchymal stromal cells in a murine model of corneal injury. Cytotherapy. 2017;19(1):28–35. doi:10.1016/j.jcyt.2016.10.007.