Treatment of Corneal Endothelial Damage in a Rabbit Model with a Bioengineered Graft Using Human Decellularized Corneal Lamina and Cultured Human Corneal Endothelium

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2019 Nov 22

PMID 31751429

Citations 11

Authors

Francisco Arnalich-Montiel

Adrian Moratilla

Sherezade Fuentes-Julian

Veronica Aparicio

Marta Cadenas Martin

Gary Peh

Jodhbir S Mehta

Khadijah Adnan

Laura Porrua

Ane Perez-Sarriegui

Maria P De Miguel

Affiliations

Soon will be listed here.

Abstract

Objective: We aimed to investigate the functionality of human decellularized stromal laminas seeded with cultured human corneal endothelial cells as a tissue engineered endothelial graft (TEEK) construct to perform endothelial keratoplasty in an animal model of corneal endothelial damage.

Methods: Engineered corneal endothelial grafts were constructed by seeding cultured human corneal endothelial cell (hCEC) suspensions onto decellularized human corneal stromal laminas with various coatings. The functionality and survival of these grafts with cultured hCECs was examined in a rabbit model of corneal endothelial damage after central descemetorhexis. Rabbits received laminas with and without hCECs (TEEK and control group, respectively).

Results: hCEC seeding over fibronectin-coated laminas provided an optimal and consistent endothelial cell count density and polygonal shape on the decellularized laminas, showing active pump fuction. Surgery was performed uneventfully as standard Descemet stripping automated endothelial keratoplasty (DSAEK). Corneal transparency gradually recovered in the TEEK group, whereas haze and edema persisted for up to 4 weeks in the controls. Histologic examination showed endothelial cells of human origin covering the posterior surface of the graft in the TEEK group.

Conclusions: Grafting of decellularized stroma carriers re-surfaced with human corneal endothelial cells ex vivo can be a readily translatable method to improve visual quality in corneal endothelial diseases.

Citing Articles

Biomedical Application of MSCs in Corneal Regeneration and Repair.

De Miguel M, Cadenas-Martin M, Stokking M, Martin-Gonzalez A Int J Mol Sci. 2025; 26(2).

PMID: 39859409 PMC: 11766311. DOI: 10.3390/ijms26020695.

Hypoxia Increases the Efficiencies of Cellular Reprogramming and Oncogenic Transformation in Human Blood Cell Subpopulations In Vitro and In Vivo.

Moratilla A, Martin D, Cadenas-Martin M, Stokking M, Quesada M, Arnalich F Cells. 2024; 13(11.

PMID: 38891103 PMC: 11172288. DOI: 10.3390/cells13110971.

Femtosecond Laser Cutting of Human Crystalline Lens Capsule and Decellularization for Corneal Endothelial Bioengineering.

Ben Moussa O, Parveau L, Aouimeur I, Egaud G, Maurin C, Fraine S Bioengineering (Basel). 2024; 11(3).

PMID: 38534529 PMC: 10968626. DOI: 10.3390/bioengineering11030255.

Three-dimensional bioprinting in ophthalmic care.

Al-Atawi S Int J Ophthalmol. 2023; 16(10):1702-1711.

PMID: 37854366 PMC: 10559024. DOI: 10.18240/ijo.2023.10.21.

Corneal Endothelial-like Cells Derived from Induced Pluripotent Stem Cells for Cell Therapy.

Ng X, Peh G, Yam G, Tay H, Mehta J Int J Mol Sci. 2023; 24(15).

PMID: 37569804 PMC: 10418878. DOI: 10.3390/ijms241512433.

References

Bednarz J, Doubilei V, Wollnik P, Engelmann K . Effect of three different media on serum free culture of donor corneas and isolated human corneal endothelial cells. Br J Ophthalmol. 2001; 85(12):1416-20. PMC: 1723804. DOI: 10.1136/bjo.85.12.1416. View

Mills R, Jones D, Winkler C, Wallace G, Wilhelmus K . Topical FK-506 prevents experimental corneal allograft rejection. Cornea. 1995; 14(2):157-60. View

Bayyoud T, Thaler S, Hofmann J, Maurus C, Spitzer M, Bartz-Schmidt K . Decellularized bovine corneal posterior lamellae as carrier matrix for cultivated human corneal endothelial cells. Curr Eye Res. 2012; 37(3):179-86. DOI: 10.3109/02713683.2011.644382. View

Mimura T, Yamagami S, Amano S . Corneal endothelial regeneration and tissue engineering. Prog Retin Eye Res. 2013; 35:1-17. DOI: 10.1016/j.preteyeres.2013.01.003. View

Proulx S, Brunette I . Methods being developed for preparation, delivery and transplantation of a tissue-engineered corneal endothelium. Exp Eye Res. 2011; 95(1):68-75. DOI: 10.1016/j.exer.2011.06.013. View

Okumura N, Sakamoto Y, Fujii K, Kitano J, Nakano S, Tsujimoto Y . Rho kinase inhibitor enables cell-based therapy for corneal endothelial dysfunction. Sci Rep. 2016; 6:26113. PMC: 4870691. DOI: 10.1038/srep26113. View

Alio Del Barrio J, El Zarif M, Azaar A, Makdissy N, Khalil C, Harb W . Corneal Stroma Enhancement With Decellularized Stromal Laminas With or Without Stem Cell Recellularization for Advanced Keratoconus. Am J Ophthalmol. 2017; 186:47-58. DOI: 10.1016/j.ajo.2017.10.026. View

Rizwan M, Peh G, Ang H, Lwin N, Adnan K, Mehta J . Sequentially-crosslinked bioactive hydrogels as nano-patterned substrates with customizable stiffness and degradation for corneal tissue engineering applications. Biomaterials. 2017; 120:139-154. DOI: 10.1016/j.biomaterials.2016.12.026. View

VAN HORN D, Sendele D, Seideman S, Buco P . Regenerative capacity of the corneal endothelium in rabbit and cat. Invest Ophthalmol Vis Sci. 1977; 16(7):597-613. View

10.

Honda N, Mimura T, Usui T, Amano S . Descemet stripping automated endothelial keratoplasty using cultured corneal endothelial cells in a rabbit model. Arch Ophthalmol. 2009; 127(10):1321-6. DOI: 10.1001/archophthalmol.2009.253. View

11.

Peh G, Ang H, Lwin C, Adnan K, George B, Seah X . Regulatory Compliant Tissue-Engineered Human Corneal Endothelial Grafts Restore Corneal Function of Rabbits with Bullous Keratopathy. Sci Rep. 2017; 7(1):14149. PMC: 5658403. DOI: 10.1038/s41598-017-14723-z. View

12.

Crapo P, Gilbert T, Badylak S . An overview of tissue and whole organ decellularization processes. Biomaterials. 2011; 32(12):3233-43. PMC: 3084613. DOI: 10.1016/j.biomaterials.2011.01.057. View

13.

Lopez-Iglesias P, Blazquez-Martinez A, Fernandez-Delgado J, Regadera J, Nistal M, De Miguel M . Short and long term fate of human AMSC subcutaneously injected in mice. World J Stem Cells. 2011; 3(6):53-62. PMC: 3158900. DOI: 10.4252/wjsc.v3.i6.53. View

14.

Alaminos M, Sanchez-Quevedo M, Munoz-Avila J, Serrano D, Medialdea S, Carreras I . Construction of a complete rabbit cornea substitute using a fibrin-agarose scaffold. Invest Ophthalmol Vis Sci. 2006; 47(8):3311-7. DOI: 10.1167/iovs.05-1647. View

15.

Rice A, Wood J, Milross C, Collins C, McCarthy N, Vowels M . Conditions that enable human hematopoietic stem cell engraftment in all NOD-SCID mice. Transplantation. 2001; 69(5):927-35. DOI: 10.1097/00007890-200003150-00044. View

16.

Fuentes-Julian S, Arnalich-Montiel F, Jaumandreu L, Leal M, Casado A, Garcia-Tunon I . Adipose-derived mesenchymal stem cell administration does not improve corneal graft survival outcome. PLoS One. 2015; 10(3):e0117945. PMC: 4346399. DOI: 10.1371/journal.pone.0117945. View

17.

Gain P, Jullienne R, He Z, Aldossary M, Acquart S, Cognasse F . Global Survey of Corneal Transplantation and Eye Banking. JAMA Ophthalmol. 2015; 134(2):167-73. DOI: 10.1001/jamaophthalmol.2015.4776. View

18.

Jackel T, Knels L, Valtink M, Funk R, Engelmann K . Serum-free corneal organ culture medium (SFM) but not conventional minimal essential organ culture medium (MEM) protects human corneal endothelial cells from apoptotic and necrotic cell death. Br J Ophthalmol. 2010; 95(1):123-30. DOI: 10.1136/bjo.2010.183418. View

19.

Stuart A, Romano V, Virgili G, Shortt A . Descemet's membrane endothelial keratoplasty (DMEK) versus Descemet's stripping automated endothelial keratoplasty (DSAEK) for corneal endothelial failure. Cochrane Database Syst Rev. 2018; 6:CD012097. PMC: 6513431. DOI: 10.1002/14651858.CD012097.pub2. View

20.

Lai J, Chen K, Hsiue G . Tissue-engineered human corneal endothelial cell sheet transplantation in a rabbit model using functional biomaterials. Transplantation. 2007; 84(10):1222-32. DOI: 10.1097/01.tp.0000287336.09848.39. View