ABSTRACT
We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients. At 1 year after surgery, the transplanted sheet remained intact, best corrected visual acuity had not improved or worsened, and cystoid macular edema was present. (Funded by Highway Program for Realization of Regenerative Medicine and others; University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000011929 .).
Subject(s)
Induced Pluripotent Stem Cells/cytology , Macular Degeneration/therapy , Retinal Pigment Epithelium/cytology , Aged , Cell Culture Techniques , Cell Differentiation , Feasibility Studies , Female , Fibroblasts , Humans , Male , Retinal Pigment Epithelium/transplantation , Transplantation, AutologousABSTRACT
Human cultured gingival epithelial sheets were used as an autologous grafting material for regenerating gingival tissue in the maxillary left and mandibular right quadrants of a patient with chronic desquamative gingivitis. Six months post-surgery in both treated areas, there were gains in keratinized gingiva and no signs of gingival inflammation compared to presurgery. In the maxillary left quadrant, preoperative histopathologic findings revealed the epithelium was separated from the connective tissue and inflammatory cells were extensive. After grafting with the gingival epithelial sheets, inflammatory cells were decreased and separation between epithelium and connective tissue was not observed. The human cultured gingival epithelial sheets fabricated using tissue engineering technology showed significant promise for gingival augmentation in periodontal therapy.
Subject(s)
Gingiva/transplantation , Gingivitis/therapy , Gingivoplasty , Tissue Engineering , Cell Culture Techniques , Chronic Disease , Epithelial Cells , Female , Humans , Middle AgedABSTRACT
BACKGROUND: It has been demonstrated that human cultured epithelial sheets prepared by tissue engineering techniques provide useful graft material for wound healing and tissue regeneration. However, limited information is available with regard to biological effects such as release of growth factors from human cultured gingival epithelial sheets (HCGES). The purpose of this study was to measure the levels of growth factors released from HCGES into culture medium. METHODS: Twenty patients aged 44 to 71 years with generalized chronic periodontitis were recruited, and their gingival tissues obtained during periodontal flap surgery. The levels of vascular endothelial growth factor (VEGF), transforming growth factor-alpha and -beta1 (TGF-alpha and -beta1), and epidermal growth factor (EGF) released into the culture medium were determined using enzyme-linked immunosorbent assay at the just confluent (T1) and the adequate stratification (T2) culture stages. The medium without cells was collected as a control (T0). Statistical tests were performed by analysis of variance and Sheffé multiple range test among T0, T1, and T2. RESULTS: Significantly higher levels of VEGF and TGF-alpha were observed at T1 and T2 compared to T0 (P<0.001). In addition, there was a significant difference in the TGF-alpha levels between T2 and T1 (P<0.001). TGF-beta1 at T1 was significantly higher in comparison to T0 (P <0.01). EGF had been released only in a small amount at T2. CONCLUSION: This study indicates that meaningful amounts of VEGF and TGF-alpha and -beta1 are released from HCGES, which suggests potential for promoting wound healing and tissue regeneration after grafting.
Subject(s)
Epithelial Cells/metabolism , Gingiva/metabolism , Growth Substances/biosynthesis , Tissue Engineering , 3T3 Cells , Adult , Aged , Analysis of Variance , Animals , Cell Culture Techniques , Cell Division , Cells, Cultured , Culture Media, Conditioned , Endothelial Growth Factors/analysis , Endothelial Growth Factors/biosynthesis , Epidermal Growth Factor/analysis , Epidermal Growth Factor/biosynthesis , Epithelial Cells/transplantation , Female , Gingiva/cytology , Growth Substances/analysis , Humans , Lymphokines/analysis , Lymphokines/biosynthesis , Male , Mice , Middle Aged , Time Factors , Transforming Growth Factor alpha/analysis , Transforming Growth Factor alpha/biosynthesis , Transforming Growth Factor beta/analysis , Transforming Growth Factor beta/biosynthesis , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth FactorsABSTRACT
BACKGROUND: It has been demonstrated that human cultured epithelial sheets prepared by tissue engineering techniques provide useful graft material for wound healing and tissue regeneration. However, limited information is available with regard to biological effects such as release of growth factors from human cultured gingival epithelial sheets (HCGES). The purpose of this study was to measure the levels of growth factors released from HCGES into culture medium Methods: Twenty patients aged 44 to 71 years with generalized chronic periodontitis were recruited, and their gingival tissues obtained during periodontal flap surgery. The levels of vascular endothelial growth factor (VEGF), transforming growth factor-α and -ßl (TGF-α and -ßl), and epidermal growth factor (EGF) released into the culture medium were determined using enzyme-linked immunosorbent assay at the just confluent (Tl) and the adequate stratification (T2) culture stages. The medium without cells was collected as a control (TO) statistical tests were performed by analysis of variance and sheffé multiple range test among TO, T1, and T2. RESULTS: Significantly higher levels of VEGF and TGF-α were observed at T1 and T2 compared to To (P<0.001). In addition, there was a significant difference in the TGF-α levels between T2 and T1 (P<0.001). TGF-ßl at T1 was significantly higher in comparison to T0 (P<0.0l). EGF had been released only in a small amount at T2. CONCLUSION: This study indicates that meaningful amounts of VEGF and TGF-α and -ßl are released from HCGES, which suggests potential for promoting wound healing and tissue regeneration after grafting. J Periodontol 2002;73:748-753.
