Cellular Substrates for Cell-Based Tissue Engineering of Human Corneal Endothelial Cells

Zhu, Qin; Sun, Hong; Yang, Dongmei; Tighe, Sean; Liu, Yongsong; Zhu, Yingting; Hu, Min

doi:10.7150/ijms.34440

Cited by 5 publications

(6 citation statements)

References 94 publications

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“…The substrate composition and topography have a crucial impact on the success of CEC culture because they stimulate the attachment, migration, proliferation, and overall function of the cultured CECs [ 17 , 61 ]. Due to the poor adherence of CECs to uncoated culture dishes, various biological, biosynthetic, or synthetic substrates for CEC expansion have been tested up to now, as reviewed elsewhere [ 62 – 64 ] (Table 1 ). The ideal substrate should mimic the composition (collagens 4–6, 8, 18, fibronectin, laminin, thrombospondin) and topography of DM [ 64 , 65 ], therefore helping to maintain the CEC phenotype and function and promoting CE regeneration after injury [ 66 ].…”

Section: In Vitro Expansion Of Cells From Donor Tissuementioning

confidence: 99%

“…It was shown that a replacement of the DM alone can be sufficient to induce the regeneration of host CECs in vivo [ 67 ]. In recent studies, an FNC coating mix® [ 11 , 40 , 45 ] and collagen 1 and 4 [ 21 , 62 , 68 ] have been the most widely used substrates for CEC cultures.…”

Section: In Vitro Expansion Of Cells From Donor Tissuementioning

confidence: 99%

“…Improve attachment and morphology of primary CECs; supposed to maintain the normal phenotype of CECs and prevent phenotypic change. Handling of soft collagen-based substrates may be improved by a cross-linking the collagen fibers [ 62 ] Laminin 5 Promotes adhesion, migration, and proliferation of human primary CECs (donor age: 55–76 years), and supports wound healing of injured CEC [ 121 ] Laminin-511, -521 Enhance adhesion, proliferation, and differentiation of human primary CECs (donor age: > 40 years) [ 122 ] Laminin E8 fragments Support human CECs’ expansion with a similar efficacy to that obtained with laminins-511/-521. Recombinant laminin fragments can be produced more easily than full-length laminins [ 53 , 122 ] FNC coating mix ® (fibronectin + collagen 1 + albumin) Improves rapid attachment of primary human CECs and reduces cell loss due to rinsing of cells.…”

Section: In Vitro Expansion Of Cells From Donor Tissuementioning

confidence: 99%

“…Several culture media have been used for CEC expansion. These media include Dulbecco’s modified Eagle’s medium (DMEM) [ 46 , 73 ], a mixture of DMEM with Ham’s F12 (F12) supplement [ 46 ], M199:F12 (1:1), also referred to as F99 medium [ 39 , 46 ], endothelial growth medium 2 [ 17 ], endothelial serum-free medium (Endo-SFM) [ 74 ], and Opti-MEM I [ 40 , 46 , 62 ], which is reduced serum minimal essential medium, enriched for insulin, transferrin, hypoxanthine, thymidine, and trace elements. Currently, the most used media for CEC proliferation are F99 and Opti-MEM I [ 40 , 46 ].…”

Section: In Vitro Expansion Of Cells From Donor Tissuementioning

confidence: 99%

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Ex vivo expansion and characterization of human corneal endothelium for transplantation: a review

2021

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The corneal endothelium plays a key role in maintaining corneal transparency. Its dysfunction is currently treated with penetrating or lamellar keratoplasty. Advanced cell therapy methods seek to address the persistent global deficiency of donor corneas by enabling the renewal of the endothelial monolayer with tissue-engineered grafts. This review provides an overview of recently published literature on the preparation of endothelial grafts for transplantation derived from cadaveric corneas that have developed over the last decade (2010–2021). Factors such as the most suitable donor parameters, culture substrates and media, endothelial graft storage conditions, and transplantation methods are discussed. Despite efforts to utilize alternative cellular sources, such as induced pluripotent cells, cadaveric corneas appear to be the best source of cells for graft preparation to date. However, native endothelial cells have a limited natural proliferative capacity, and they often undergo rapid phenotype changes in ex vivo culture. This is the main reason why no culture protocol for a clinical-grade endothelial graft prepared from cadaveric corneas has been standardized so far. Currently, the most established ex vivo culture protocol involves the peel-and-digest method of cell isolation and cell culture by the dual media method, including the repeated alternation of high and low mitogenic conditions. Culture media are enriched by additional substances, such as signaling pathway (Rho-associated protein kinase, TGF-β, etc.) inhibitors, to stimulate proliferation and inhibit unwanted morphological changes, particularly the endothelial-to-mesenchymal transition. To date, this promising approach has led to the development of endothelial grafts for the first in-human clinical trial in Japan. In addition to the lack of a standard culture protocol, endothelial-specific markers are still missing to confirm the endothelial phenotype in a graft ready for clinical use. Because the corneal endothelium appears to comprise phenotypically heterogeneous populations of cells, the genomic and proteomic expression of recently proposed endothelial-specific markers, such as Cadherin-2, CD166, or SLC4A11, must be confirmed by additional studies. The preparation of endothelial grafts is still challenging today, but advances in tissue engineering and surgery over the past decade hold promise for the successful treatment of endothelial dysfunctions in more patients worldwide.

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Section: In Vitro Expansion Of Cells From Donor Tissuementioning

confidence: 99%

Section: In Vitro Expansion Of Cells From Donor Tissuementioning

confidence: 99%

Section: In Vitro Expansion Of Cells From Donor Tissuementioning

confidence: 99%

Section: In Vitro Expansion Of Cells From Donor Tissuementioning

confidence: 99%

See 2 more Smart Citations

Ex vivo expansion and characterization of human corneal endothelium for transplantation: a review

2021

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“…Here, we will specifically emphasize the development of cornea mimics that use cells in combination with natural biomaterials that explore patient outcomes in animal models or serve as in vitro tissue models. Many cell types have been investigated for use in corneal tissue engineering, including corneal endothelial cells (CEnCs), corneal epithelial cells (CEpCs), corneal epithelial stem cells (CEpSCs), keratocytes (CKs), mesenchymal stem cells (MSCs), adipose-tissue derived stem cells (ASCs), and embryonic-derived stem cells [ 132 , 133 , 134 ].…”

Section: Engineering a Cornea Mimetic: Cell Types And Their Functionmentioning

confidence: 99%

Recent Advances in Natural Materials for Corneal Tissue Engineering

et al. 2021

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Given the incidence of corneal dysfunctions and diseases worldwide and the limited availability of healthy, human donors, investigators are working to generate engineered cellular and acellular therapeutic approaches as alternatives to corneal transplants from human cadavers. These engineered strategies aim to address existing complications with human corneal transplants, including graft rejection, infection, and complications resulting from surgical methodologies. The main goals of these research endeavors are to (1) determine ideal mechanical properties, (2) devise methodologies to improve the efficacy of engineered corneal grafts and cell-based therapies, and (3) optimize transplantation of engineered tissue structures in the eye. Thus, recent innovations have sought to address these challenges through both in vitro and in vivo studies. This review covers recent work aimed at evaluating engineered materials, potential therapeutic cells, and the resulting cell-material interactions that lead to optimal corneal graft properties. Furthermore, we discuss promising strategies in corneal tissue engineering techniques and in vivo studies in animal models.

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Corneal tissue engineering: From research to industry, quality of life impact, and Latin American ophthalmologists' perspectives

Rodríguez Fuentes,

Flores Nucamendi,

Valdez-García

et al. 2024

F1000Res

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Background Tissue engineering research aims to address the global shortage of donated corneal tissue, yet challenges persist in clinical translation. This study assesses the pathway from basic research to clinical adoption in corneal tissue engineering. Methods Bibliometric and patent analyses were conducted using the Web of Science-Core Collection and Lens databases to identify top authors, countries, journals, publication trends, inventors, patent statuses, and affiliated companies. A quality-adjusted life year (QALY) analysis compared engineered corneal endothelium to full keratoplasty. A pilot study surveyed thirty ophthalmologist surgeons from eight Latin American countries. Results A strong upward publication trend (R2 = 0.89, p = 1.53x10^-9) in corneal endothelium engineering was observed over the past decade, led by the USA, China, and Japan. Among 614 research papers, 26 patents and 10 companies were identified. Engineered corneal endothelium showed a QALY gain of 0.74 versus 0.07 of corneal transplants. Most survey respondents (97%) expressed interest in adopting engineered corneal endothelium for transplantation if affordability, biocompatibility, and functionality were assured. Conclusions While tissue engineering offers promise in alleviating corneal scarcity, a significant gap remains between scientific advancements and clinical adoption, presenting “death valleys.” Addressing this requires more efficient navigation of the interplay between scientific progress, technology adoption, and clinical practice.

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Cellular Substrates for Cell-Based Tissue Engineering of Human Corneal Endothelial Cells

Cited by 5 publications

References 94 publications

Ex vivo expansion and characterization of human corneal endothelium for transplantation: a review

Ex vivo expansion and characterization of human corneal endothelium for transplantation: a review

Recent Advances in Natural Materials for Corneal Tissue Engineering

Corneal tissue engineering: From research to industry, quality of life impact, and Latin American ophthalmologists' perspectives

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