Human Corneal Endothelial Cell Expansion for Corneal Endothelium Transplantation: An Overview

Abstract

The monolayer of cells forming the human corneal endothelium is critical to the maintenance of corneal transparency and is not known to regenerate in vivo. Thus, dysfunction of these cells constitutes the most often cited reasons for the 150,000 or so corneal transplants performed yearly. Although current corneal transplantation is more than 90% successful at 1 year, longer term results are not as encouraging with approximately 70% success at 5 years. Nonimmunologic graft failure and allograft endothelial rejection are the main problems. Furthermore, the global shortage of donor corneas greatly restricts several corneal transplantations performed. With advances in understanding corneal endothelial cell biology, it is now possible to cultivate human corneal endothelial cells (HCECs) in vitro, thus providing new opportunities to develop novel tissue-engineered human corneal endothelium. This review will provide an overview of (a) the characteristics of human corneal endothelium; (b) past and present HCECs isolation and culture protocols; (c) various potential carriers for the generation of tissue-engineered corneal endothelium, together with some of the functional studies reported in various animal models; and (d) the current rapid advancements in surgical techniques for keratoplasty. A successful combination of tissue-engineered human corneal endothelium coupled with innovative and groundbreaking surgical procedures will bridge basic research involving cultured HCECs, bringing it from bench to bedside.

Propagation of Human Corneal Endothelial Cells: A Novel Dual Media Approach

“…It is known that corneal endothelial cells (CECs) are arrested in the G 1 phase of the cell cycle and do not undergo active cellular regeneration within the eye (26,27). Hence, in situations where they become damaged or the cell density falls below a critical threshold, the functional dynamics of the corneal endothelium will be compromised (41). This leads to a cascade of pathological events, beginning with stromal edema, corneal clouding, and a loss of visual acuity, which will eventually result in corneal blindness.…”

Characterization of cryopreserved primary human corneal endothelial cells cultured in human serum-supplemented media

“…The development in surgical treatment of corneal endothelial diseases, with progressive thinning of grafts and its related advantages (13,14) , leads us to conclude that transplantation with cultured en- dothelial cells may represent the next advance in this field (2)(3)(4)(5)(6)(7)(8)(9) . Animal studies have demonstrated promising results (15,16) .…”

“…Since Stocker et al (1) established a human corneal endothelial cell (HCEC) culture, the potential for cell therapy to treat corneal endothelial dysfunction using HCECs has demonstrated continuous development (2)(3)(4)(5)(6)(7)(8) . The limitations associated with this therapy can be basically divided into two major areas: those related to culturing the cells, such as proliferation, cellular senescence, and fibroblastic transformation and those related to the logistics and techniques for transplanting the cells (2)(3)(4)(5)(6)(7)(8) .…”

“…The limitations associated with this therapy can be basically divided into two major areas: those related to culturing the cells, such as proliferation, cellular senescence, and fibroblastic transformation and those related to the logistics and techniques for transplanting the cells (2)(3)(4)(5)(6)(7)(8) .…”

Cytotoxicity of Lidocaine to Human Corneal Endothelial Cells In Vitro

“…Results suggest that lidocaine above 1.25 g/l reduced cellular viability and triggered apoptosis in HCE cells in a time-and dose-dependent manner. Diminishment of DΨm and the activation of caspases indicate that lidocaine-induced apoptosis was caspase dependent and may be related to mitochondrial pathway.Human corneal endothelium (HCE), a functional monolayer forming the demarcation between cornea and anterior chamber, plays pivotal roles in maintaining corneal transparency by regulating corneal stromal water content [1]. Notwithstanding the evidence of proliferation when deprived of their nature environment, HCE cells are trapped in the G1 phase of the cell cycle and have a limited, if not restricted, proliferative capacity in vivo [2,3], accompanied by an annual attrition rate of 0.3-0.6% in cell density during adulthood [4].…”