Results of a phase I/II clinical trial: standardized, non-xenogenic, cultivated limbal stem cell transplantation

Autor: Zwi N. Berneman, Carina Koppen, Inge Leysen, Nadia Zakaria, Jean-Pierre Timmermans, Tine Possemiers, Marie-José Tassignon, Sorcha Ní Dhubhghaill, Jos J. Rozema
Přispěvatelé: Ophtalmology - Eye surgery
Rok vydání: 2014
Předmět:
Male
genetic structures
Limbal epithelial stem cells
Visual Acuity
Progenitor cells
Tissue specific stem cells
Corneal Diseases
Cell therapy
Composite grafts
Stem Cells/cytology
Limbal stem cell
Child
Cells
Cultured
Medicine(all)
Stem Cells
General Medicine
Middle Aged
Flow Cytometry
Clinical trial
Treatment Outcome
surgical procedures
operative
Female
Stem cell
SHEM
Corneal Diseases/physiopathology
Ocular surface reconstruction
Adult stem cell
Adult
medicine.medical_specialty
Adolescent
Transplantation
Heterologous
Cellular therapy
Amniotic membrane
Corneal opacity
Limbus Corneae
Biology
Epithelial Cells/cytology
General Biochemistry
Genetics and Molecular Biology
Young Adult
CNT-20
Preoperative Care
medicine
Animals
Humans
Amnion
Limbus Corneae/cytology
Progenitor cell
Aged
Cell Proliferation
Postoperative Care
Biochemistry
Genetics and Molecular Biology(all)
Research
Corneal neovascularization
Amnion/cytology
Reproducibility of Results
Epithelial Cells
Somatic stem cells
Corneal reconstruction
medicine.disease
eye diseases
Surgery
Limbal stem cell transplantation
Transplantation
Tissue regeneration
Human medicine
Cell culture
sense organs
Cell transplantation
Stem Cell Transplantation
Zdroj: Journal of Translational Medicine
Journal of translational medicine
ISSN: 1479-5876
DOI: 10.1186/1479-5876-12-58
Popis: Background To determine if a standardized, non-xenogenic, reduced manipulation cultivation and surgical transplantation of limbal stem cell grafts is a safe and effective treatment option for patients with total and partial limbal stem cell deficiency. Methods In vitro cellular outgrowth and phenotype of the limbal epithelial cell and composite grafts were validated using a new protocol. Patients received either autologous (n = 15) or allogenic (n = 3) explants cultured using a standardized protocol free from xenogenic products. The resulting grafts were transplanted using a reduced manipulation surgical technique. Results The majority of cells (>50%) displayed a progenitor phenotype typified by positive immunofluorescence for ∆Np63, CK14 and ABCG2 and low immunofluorescence for CK3/12 and desmoglein 3 proteins. The surgical protocol was designed to minimize manipulation and the graft itself was secured without sutures. The transplant recipients were followed for a mean of 24 months. Twelve of the 18 transplant recipients were graded as anatomically successful (67%), based on the defined success parameters. There was a significant reduction in corneal neovascularization, which was accompanied by an improvement in pain though not photophobia or central corneal opacity post transplant. The transplantation protocol showed no measureable effect on visual acuity. Conclusion We conclude that this standardized culture system and surgical approach is safe and effective in reducing corneal neovascularization. The technique is free from animal contaminants and maintains a large proportion of progenitor cells. Although this technique did not improve visual function, restoring a functional epithelial cell layer and reducing corneal neovascularization provides an improved platform for a penetrating keratoplasty to ultimately improve visual function.
Databáze: OpenAIRE
Externí odkaz: