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

Oie, Yoshinori; Sugita, Seiichiro; Yokokura, Shunji; Nakazawa, Toru; Tomida, Daisuke; Satake, Yoshiyuki; Shimazaki, Jun; Hara, Yuko; Shiraishi, Atsushi; Quantock, Andrew J.; Ogasawara, Takahiro; Inoie, Masukazu; Nishida, Kohji

doi:10.1016/j.ophtha.2023.01.016

Cited by 10 publications

(4 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The approval and commercialization of the first human somatic stem cell product for ophthalmic use, in 2015, was Holoclar ® . Following that, Nepic ® and Ocural ® were released in Japan after a government-controlled clinical trial [46,47]. The study adhered to the stipulations of good clinical practice within a well-defined clinical protocol, and strict quality control measures were implemented for the fabrication of cell sheets in a facility compliant with good manufacturing practice (GMP) standards.…”

Section: Discussionmentioning

confidence: 99%

“…Oral mucosal epithelial cells were isolated and, after enzymatic treatment, seeded on 3T3-derived feeder cells and subjected to subcultures. Once sufficient expansion of the epithelial cells on temperatureresponsive cell-culture dishes was confirmed, sheet transplantation was scheduled for at least four weeks later [17,47].…”

Section: Culturing and Sheet Fabricationmentioning

confidence: 99%

“…On 11 June 2021, the first-ever COMET product for the treatment of LSCD, named Ocural ® , was approved as a regenerative medicine product by the Pharmaceuticals and Medical Devices Agency, the regulatory agency in Japan responsible for the approval and supervision of pharmaceuticals and medical devices [46]. However, the first regenerative medicine product manufactured with this temperature-responsive cultivation technique for ophthalmic use, which was approved in Japan, was a non-COMET, human autologous limbal epithelial cell sheet product [46,47]. Nepic ® was launched on 19 March 2020, specifically for the treatment of unilateral LSCD.…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, Ocural ® is indicated for bilateral LSCD. Ocural ® is composed of a cultivated oral mucosal epithelium package and a tissue transportation set consisting of tubes used to transport oral mucosal tissue, harvested at a medical institution, and blood [47,48]. The second COMET product, Sakracy ® , was introduced into the Japanese market on 20 January 2022.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Early Clinical Outcomes of the First Commercialized Human Autologous Ex Vivo Cultivated Oral Mucosal Epithelial Cell Transplantation for Limbal Stem Cell Deficiency: Two Case Reports and Literature Review

Toshida

Kasahara

Kiriyama

et al. 2023

IJMS

View full text Add to dashboard Cite

The first product in the world for ex vivo cultivated oral mucosal epithelial cell transplantation (COMET) to treat limbal stem cell deficiency (LSCD), named Ocural®, was launched in June 2021 in Japan. COMET was performed on two patients, including the first case in the post-marketing phase of Ocural®. Pathological and immunohistochemical examinations were also carried out using specimens obtained before and after COMET and the spare cell sheet. In case 1, the ocular surface remained free from epithelial defects for approximately six months. In case 2, although defect of the cornea-like epithelia was observed after COMET for one month, it was resolved after the insertion of lacrimal punctal plugs. In case 1, adjuvant treatment was interrupted due to an accident during the second month after COMET, resulting in conjunctival ingrowth and corneal opacity. Eventually, a lamellar keratoplasty was required at six months after COMET. Immunohistochemistry revealed the presence of markers for stem cells (p63, p75), proliferation (Ki-67), and differentiation (Keratin-3, -4, and -13) in both the cornea-like tissue after COMET and a cultivated oral mucosal epithelial cell sheet. In conclusion, Ocural® can be accomplished without major complications, and the stem cells derived from oral mucosa might be successfully engrafted.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Culturing and Sheet Fabricationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Early Clinical Outcomes of the First Commercialized Human Autologous Ex Vivo Cultivated Oral Mucosal Epithelial Cell Transplantation for Limbal Stem Cell Deficiency: Two Case Reports and Literature Review

Toshida

Kasahara

Kiriyama

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

Biologicals and Biomaterials for Corneal Regeneration and Vision Restoration in Limbal Stem Cell Deficiency

Di Girolamo

2024

Advanced Materials

View full text Add to dashboard Cite

The mammalian cornea is decorated with stem cells bestowed with the life‐long task of renewing the epithelium, provided they remain healthy, functional and in sufficient numbers. If not, a debilitating disease known as limbal stem cell deficiency (LSCD) can develop causing blindness. Decades after the first stem cell (SC) therapy was devised to treat this condition, patients continue to suffer unacceptable failures. During this time, improvements to therapeutics have included identifying better markers to isolate robust SC populations and nurturing them on crudely modified biological or biomaterial scaffolds including human amniotic membrane, fibrin and contact lenses, prior to their delivery. Researchers are now gathering information about the biomolecular and biomechanical properties of the corneal SC niche to decipher what biological and/or synthetic materials can be incorporated into these carriers. Advances in biomedical engineering including electrospinning and 3D bioprinting with surface functionalization and micropatterning, and self‐assembly models, have generated a wealth of biocompatible, biodegradable, integrating scaffolds to choose from, some of which are being tested for their SC delivery capacity in the hope of improving clinical outcomes for patients with LSCD.This article is protected by copyright. All rights reserved

show abstract

Biomolecule-based hydrogels as delivery systems for limbal stem cell transplantation: A review

Wang,

Xu,

Zhou

et al. 2024

International Journal of Biological Macromolecules

View full text Add to dashboard Cite

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

Cited by 10 publications

References 17 publications

Early Clinical Outcomes of the First Commercialized Human Autologous Ex Vivo Cultivated Oral Mucosal Epithelial Cell Transplantation for Limbal Stem Cell Deficiency: Two Case Reports and Literature Review

Early Clinical Outcomes of the First Commercialized Human Autologous Ex Vivo Cultivated Oral Mucosal Epithelial Cell Transplantation for Limbal Stem Cell Deficiency: Two Case Reports and Literature Review

Biologicals and Biomaterials for Corneal Regeneration and Vision Restoration in Limbal Stem Cell Deficiency

Biomolecule-based hydrogels as delivery systems for limbal stem cell transplantation: A review

Contact Info

Product

Resources

About