title: Carrier-free cultured autologous oral mucosa epithelial cell sheet (CAOMECS) for corneal epithelium reconstruction: a histological study.
abstract: This study investigates the therapeutic effects of carrier-free cultured autologous oral mucosa epithelial cell sheet (CAOMECS) transplantation for experimentally induced severe rabbit limbal stem cell deficiency (LSCD). Buccal biopsies were performed and CAOMECS were cultured and transplanted onto diseased corneas. Six-month follow-up examinations indicated that three out of four corneas with CAOMECS grafts showed a decrease in superficial vascularization, while almost all the sham corneas did not show a similar decrease. H&E staining of corneas showed that CAOMECS transplantation reduced blood vessel invasion of central cornea, reduced lymphocyte infiltration and fibrotic tissue formation. DeltaNp63 stained markedly in the grafted cornea and to a lesser extent in the sham corneas. PCNA and Ki-67 staining were much greater in the sham corneas than in the grafted and normal corneas. K3 and K13 staining demonstrated that CAOMECS transplanted corneas had much more K3- and less K13- positive cells compared to the sham corneas. Muc5AC was decreased in the central region of grafted corneas. Very little alpha-smooth muscle actin (aSMA) staining was detected in grafted corneas, while there was a greater amount of aSMA staining in sham corneas. Staining for anti-angiogenic factor TIMP -3 was also increased, and pro-angiogenic factor MMP-3 was decreased in grafted corneas compared to sham corneas. Our results indicate that CAOMECS grafts resulted in improved epithelialization of the corneal surface and decreased vascularization and fibrosis of the diseased corneas.
authors.affiliation: Department of Medicine, LA BioMed at Harbor UCLA Medical Center, Torrance, CA, USA. Electronic address: fgorce@labiomed.org.
authors.forename: Fawzia
authors.initials: F
authors.lastname: Bardag-Gorce
authors.affiliation: Department of Medicine, LA BioMed at Harbor UCLA Medical Center, Torrance, CA, USA.
authors.forename: Joan
authors.initials: J
authors.lastname: Oliva
authors.affiliation: Emmaus Life Sciences, Inc. 21250 Hawthorne Blvd. Suite 800 Torrance, CA 90503.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wood
authors.affiliation: Division of Ophthalmology, LA BioMed at Harbor UCLA Medical Center, Torrance, CA, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Hoft
authors.affiliation: Department of Medicine, LA BioMed at Harbor UCLA Medical Center, Torrance, CA, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Pan
authors.affiliation: Department of Medicine, LA BioMed at Harbor UCLA Medical Center, Torrance, CA, USA.
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Thropay
authors.affiliation: Department of Medicine, LA BioMed at Harbor UCLA Medical Center, Torrance, CA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Makalinao
authors.affiliation: Department of Pathology, LA BioMed at Harbor UCLA Medical Center, Torrance, CA, USA.
authors.forename: Samuel W
authors.initials: SW
authors.lastname: French
authors.affiliation: Department of Medicine, LA BioMed at Harbor UCLA Medical Center, Torrance, CA, USA; Emmaus Life Sciences, Inc. 21250 Hawthorne Blvd. Suite 800 Torrance, CA 90503.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Niihara
mesh_terms: D000818:Animals; D002057:Burns, Chemical / Q000473:pathology / Q000601:surgery*; D002478:Cells, Cultured; D065306:Corneal Injuries / Q000473:pathology / Q000601:surgery*; D004195:Disease Models, Animal; D019573:Epithelium, Corneal / Q000293:injuries / Q000601:surgery*; D009061:Mouth Mucosa / Q000637:transplantation*; D011817:Rabbits; D019651:Plastic Surgery Procedures / Q000379:methods*; D033581:Stem Cell Transplantation / Q000379:methods*; D014182:Transplantation, Autologous
keywords: cell sheet; corneal reconstruction; cultured autologous oral mucosa epithelial cell sheet (CAOMECS); epithelium; limbal stem cell deficiency; mucosal epithelial cells; oral mucosal epithelium; tissue engineering