Systematic review of clinical research on regenerative medicine for the cornea

Oie, Yoshinori; Komoto, Shimpei; Kawasaki, Ryo

doi:10.1007/s10384-021-00821-z

Cited by 10 publications

(9 citation statements)

References 63 publications

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“…LSCD is a severe condition causing cornea opacification, conjunctival pannus, and blindness that can be secondary to chemical or thermal injuries, autoimmune diseases such as the Stevens-Johnson syndrome, mucous membrane pemphigoid, and hereditary diseases such as aniridia [43]. Current treatments are challenging, especially in cases with structural damage of the limbal area, which is not a candidate to cell therapy.…”

Section: Discussionmentioning

confidence: 99%

Generation of a Biomimetic Substitute of the Corneal Limbus Using Decellularized Scaffolds

et al. 2021

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Patients with severe limbal damage and limbal stem cell deficiency are a therapeutic challenge. We evaluated four decellularization protocols applied to the full-thickness and half-thickness porcine limbus, and we used two cell types to recellularize the decellularized limbi. The results demonstrated that all protocols achieved efficient decellularization. However, the method that best preserved the transparency and composition of the limbus extracellular matrix was the use of 0.1% SDS applied to the half-thickness limbus. Recellularization with the limbal epithelial cell line SIRC and human adipose-derived mesenchymal stem cells (hADSCs) was able to generate a stratified epithelium able to express the limbal markers p63, pancytokeratin, and crystallin Z from day 7 in the case of SIRC and after 14–21 days of induction when hADSCs were used. Laminin and collagen IV expression was detected at the basal lamina of both cell types at days 14 and 21 of follow-up. Compared with control native limbi, tissues recellularized with SIRC showed adequate picrosirius red and alcian blue staining intensity, whereas limbi containing hADSCs showed normal collagen staining intensity. These preliminary results suggested that the limbal substitutes generated in this work share important similarities with the native limbus and could be potentially useful in the future.

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Section: Discussionmentioning

confidence: 99%

Generation of a Biomimetic Substitute of the Corneal Limbus Using Decellularized Scaffolds

et al. 2021

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“…We conducted the world's first prospective, multi-center, government-controlled pivotal clinical trial of cultivated limbal epithelial cell sheets transplanted to the eyes of patients with J o u r n a l P r e -p r o o f LSCD. Although similar clinical studies have been conducted, [10][11][12] no clinical trial has been performed that adhered to the GCP stipulations within a defined clinical protocol and the use of strict quality control for cell sheets fabricated in a GMP-grade facility. Our data, including the trial results reported here, were reviewed by the Ministry of Health, Labour and Welfare in Japan.…”

Section: Discussionmentioning

confidence: 99%

“…6,7 Conversely, cultivated limbal stem cells have been successfully used for ocular surface reconstruction in patients with unilateral LSCD, 8,9 and it is expected that this surgical approach will become more widely used as the cell sheets become more readily available. Other clinical studies have described the use of ex vivo expanded limbal epithelial cells to treat LSCD, [10][11][12] but all these studies had limitations in that they either had a retrospective single-center study design or heterogeneity among transplanted cells because of the lack of evaluation under defined shipment criteria. More importantly, no clinical trial has been performed that adhered to Good Clinical Practice (GCP) stipulations within a defined clinical protocol and the use of strict quality control for cell sheets fabricated in a Good Manufacturing Practice (GMP)-grade facility.…”

Section: Introductionmentioning

confidence: 99%

Clinical Trial of Autologous Cultivated Limbal Epithelial Cell Sheet Transplantation for Patients with Limbal Stem Cell Deficiency

Oie¹,

Sugita²,

Yokokura³

et al. 2023

Ophthalmology

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“…Tissue sections were evaluated using the histological grading score described by Mankin [ 35 ], which was modified as described previously [ 28 ]. The total score ranges from 0 to 14 and includes scores from four categories: cartilage structure, cellular abnormality, matrix staining, and tidemark integrity.…”

Section: Methodsmentioning

confidence: 99%

“…We believed that a feasible approach to overcome these setbacks is to use cell sheet technology. The use of cell sheets has been described in regenerative medicine applications, including the regeneration of myocardium [ 27 ], cornea [ 28 ], and renal tissues [ 29 ]. Recently, this technology has also been used to develop chondrocytes sheet for the repair of AC defects.…”

Section: Introductionmentioning

confidence: 99%

Zonal-Layered Chondrocyte Sheets for Repairment of Full-Thickness Articular Cartilage Defect: A Mini-Pig Model

Shen

Chou

et al. 2021

Biomedicines

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The cell sheet technique is a promising approach for tissue engineering, and the present study is aimed to determine a better configuration of cell sheets for cartilage repair. For stratified chondrocyte sheets (S-CS), articular chondrocytes isolated from superficial, middle, and deep zones were stacked accordingly. Heterogeneous chondrocyte sheets (H-CS) were obtained by mixing zonal chondrocytes. The expressions of chondrocytes, cytokine markers, and glycosaminoglycan (GAG) production were assessed in an in vitro assay. The curative effect was investigated in an in vivo porcine osteochondral defect model. The S-CS showed a higher cell viability, proliferation rate, expression of chondrogenic markers, secretion of tissue inhibitor of metalloproteinase, and GAG production level than the H-CS group. The expressions of ECM destruction enzyme and proinflammatory cytokines were lower in the S-CS group. In the mini-pigs articular cartilage defect model, the S-CS group had a higher International Cartilage Repair Society (ICRS) macroscopic score and displayed a zonal structure that more closely resembled the native cartilage than those implanted with the H-CS. Our study demonstrated that the application of the S-CS increased the hyaline cartilage formation and improved the surgical outcome of chondrocyte implication, offering a better tissue engineering strategy for treating articular cartilage defects.

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Systematic review of clinical research on regenerative medicine for the cornea

Cited by 10 publications

References 63 publications

Generation of a Biomimetic Substitute of the Corneal Limbus Using Decellularized Scaffolds

Generation of a Biomimetic Substitute of the Corneal Limbus Using Decellularized Scaffolds

Clinical Trial of Autologous Cultivated Limbal Epithelial Cell Sheet Transplantation for Patients with Limbal Stem Cell Deficiency

Zonal-Layered Chondrocyte Sheets for Repairment of Full-Thickness Articular Cartilage Defect: A Mini-Pig Model

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