Human corneal endothelial cells grafts to replace cadaveric donor corneas

Cadaveric Donor ◽

The Future ◽

Limbal Stem Cell Transplantation ◽

Donor Corneas

Human corneal endothelial cells (HCEC) grafts to replace cadaveric donor corneas have made tremendous progress in recent years, and this article highlights the most recent discoveries and important achievements in this area. Cell injection therapy with cultured HCEC has just finished its first clinical research, which showed promising results. This follows on the heels of the success of autologous limbal stem cell transplantation in bioengineered ocular tissue transplantation. Transplantation techniques like bioengineered endothelium sheet transplantation and full-thickness corneal transplantation are likely to become more prevalent in the future decade. This goal will be achieved by a combination of current advancements in HCEC propagation, high-quality culture media, and 3D or 4D tissue culture, which will be the trend in the future.

The Effects of Different Culture Media on Human Corneal Endothelial Cells

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.14-14564 ◽

2014 ◽

Vol 55 (8) ◽

pp. 5099 ◽

Cited By ~ 17

Author(s):

Eunbi Kim ◽

Jin Joo Kim ◽

Joon Young Hyon ◽

Eui-Sang Chung ◽

Tae-Young Chung ◽

...

Keyword(s):

Endothelial Cells ◽

Culture Media ◽

Human Corneal Endothelial Cells

Cultivation of Human Corneal Endothelial Cells Isolated from Paired Donor Corneas

PLoS ONE ◽

10.1371/journal.pone.0028310 ◽

2011 ◽

Vol 6 (12) ◽

pp. e28310 ◽

Cited By ~ 88

Author(s):

Gary S. L. Peh ◽

Kah-Peng Toh ◽

Fei-Yi Wu ◽

Donald T. Tan ◽

Jodhbir S. Mehta

Keyword(s):

Endothelial Cells ◽

Donor Corneas

Directed Differentiation of Human Corneal Endothelial Cells From Human Embryonic Stem Cells by Using Cell-Conditioned Culture Media

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.17-23627 ◽

2018 ◽

Vol 59 (7) ◽

pp. 3028 ◽

Cited By ~ 4

Author(s):

Xiaoniao Chen ◽

Lingling Wu ◽

Zongjin Li ◽

Ying Dong ◽

Xuetao Pei ◽

...

Keyword(s):

Stem Cells ◽

Endothelial Cells ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Culture Media ◽

Embryonic Stem ◽

Directed Differentiation ◽

Human Corneal Endothelial Cells

Effect of three different media on serum free culture of donor corneas and isolated human corneal endothelial cells

British Journal of Ophthalmology ◽

10.1136/bjo.85.12.1416 ◽

2001 ◽

Vol 85 (12) ◽

pp. 1416-1420 ◽

Cited By ~ 30

Author(s):

J. Bednarz

Keyword(s):

Endothelial Cells ◽

Serum Free ◽

Donor Corneas

SIRT1 Activation Using CRISPR/dCas9 Promotes Regeneration of Human Corneal Endothelial Cells through Inhibiting Senescence

Antioxidants ◽

10.3390/antiox9111085 ◽

2020 ◽

Vol 9 (11) ◽

pp. 1085

Author(s):

Hye Jun Joo ◽

Dae Joong Ma ◽

Jin Sun Hwang ◽

Young Joo Shin

Keyword(s):

Endothelial Cells ◽

Corneal Transplantation ◽

Corneal Edema ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Associated Proteins ◽

Activation Therapy

Human corneal endothelial cells (hCECs) are restricted in proliferative capacity in vivo. Reduction in the number of hCEC leads to persistent corneal edema requiring corneal transplantation. This study demonstrates the functions of SIRT1 in hCECs and its potential for corneal endothelial regeneration. Cell morphology, cell growth rates and proliferation-associated proteins were compared in normal and senescent hCECs. SIRT1 was activated using the CRISPR/dCas9 activation system (SIRT1a). The plasmids were transfected into CECs of six-week-old Sprague–Dawley rats using electroporation and cryoinjury was performed. Senescent cells were larger, elongated and showed lower proliferation rates and lower SIRT1 levels. SIRT1 activation promoted the wound healing of CECs. In vivo transfection of SIRT1a promoted the regeneration of CECs. The proportion of the S-phase cells was lower in senescent cells and elevated upon SIRT1a activation. SIRT1 regulated cell proliferation, proliferation-associated proteins, mitochondrial membrane potential, and oxidative stress levels. In conclusion, corneal endothelial senescence is related with a decreased SIRT1 level. SIRT1a promotes the regeneration of CECs by inhibiting cytokine-induced cell death and senescence. Gene function activation therapy using SIRT1a may serve as a novel treatment strategy for hCEC diseases.

In Vitro Evaluation and Transplantation of Human Corneal Endothelial Cells Cultured on Biocompatible Carriers

Cell Transplantation ◽

10.1177/0963689720923577 ◽

2020 ◽

Vol 29 ◽

pp. 096368972092357 ◽

Cited By ~ 1

Author(s):

Daniele Spinozzi ◽

Alina Miron ◽

Jessica T. Lie ◽

Mehrdad Rafat ◽

Neil Lagali ◽

...

Keyword(s):

Endothelial Cells ◽

Reference Model ◽

Corneal Transplantation ◽

Effective Treatment Option ◽

Human Donor ◽

Descemet Membrane ◽

Anterior Lens Capsule

Corneal transplantation is currently the only effective treatment option for dysfunctional corneal endothelial cells (CEC). In this study, we test in vitro the surgical potential of cultivated human corneal endothelial cells (hCEC) on human anterior lens capsule (HALC), LinkCell™ bioengineered collagen sheets of 20-µm thickness (LK20), and denuded Descemet membrane (dDM) as tissue-engineered grafts for Descemet membrane (DM) endothelial keratoplasty (DMEK) to bypass the problem of donor tissue availability. Primary hCEC cultured on all carriers formed a monolayer of tightly packed cells with a high cell viability rate (96% ± 4%). hCEC on HALC and LK20 showed unremarkable expression of zonula occludens-1 (ZO-1) and Na+/K+-adenosine triphosphatase (ATPase), while Na+/K+-ATPase expression of cells seeded on dDM was mainly cytoplasmic. All hCEC–carrier constructs were evaluated by simulating DMEK surgery in vitro using a human donor cornea without DM mounted on an artificial anterior chamber (AC) and a regular DMEK-graft used as a surgical reference model. During in vitro surgery, hCEC–HALC constructs behaved most similarly to a DMEK-graft during implantation and unfolding, showing good adhesion to the bare stroma. On the other hand, hCEC–LK20 and hCEC–dDM constructs required some additional handling because of challenges related to the surgical procedure, although they were both successfully unfolded and implanted in the artificial AC. The hCEC–dDM constructs showed similar graft adherence as hCEC–HALC constructs, while adherence of hCEC–LK20 constructs was less effective. After the in vitro surgery, the estimated area populated by viable cells on the hCEC–HALC and hCEC–LK20 constructs was ∼83% and ∼67%, respectively. Overall, hCEC–HALC constructs behaved most similarly to a DMEK-graft during in vitro DMEK surgery, while graft adhesion and surgical handling, respectively, are parameters still requiring optimization for hCEC–LK20 and hCEC–dDM constructs.