Ocular Surface Reconstruction Using Autologous Rabbit Oral Mucosal Epithelial Sheets Fabricated Ex Vivo on a Temperature-Responsive Culture Surface

Hayashida, Yasutaka; Nishida, Kohji; Yamato, Masayuki; Watanabe, Katsuhiko; Maeda, Naoyuki; Watanabe, Hitoshi; Kikuchi, Akihiko; Okano, Teruo; Tano, Yasuo

doi:10.1167/iovs.04-0813

Cited by 122 publications

(91 citation statements)

References 37 publications

(35 reference statements)

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“…23,24 As the cultures were not air-lifted, epithelial stratification was less then reported earlier, 25,26 and the cells appeared generally flatter. Interestingly, transcription factor p63, 11 and notably low affinity NGF receptor p75, 27 the progenitor cell markers known to be expressed by oral mucosal epithelial cells were both found in the cultures, along with the expression of ABCG2.…”

Section: Discussionmentioning

confidence: 81%

Transplantation of cultivated oral mucosal epithelial cells for severe corneal burn

Kuo

et al. 2009

Eye

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Purpose To access the feasibility of using cultivated oral mucosal epithelial cell transplantation (COMET) for the management of severe corneal burn. Methods COMET was performed to promote re-epithelialization in two eyes with acute alkaline burn and one eye with chronic alkaline burn, and to reconstruct the ocular surface in two eyes with chronic thermal burn. Autologous oral mucosal epithelial cells obtained from biopsy were cultivated on amniotic membrane. Immunoconfocal microscopy for keratins and progenitor cell markers was performed to characterize the cultivated epithelial sheet. Following transplantation, the clinical outcome and possible complications were documented. The patients were followed for an averaged 29.6 ± 3.6 (range: 26-34) months. Results Cultivated oral mucosal epithelial sheet expressed keratin 3, 13, and progenitor cell markers p63, p75, and ABCG2. After COMET, all the corneas became less inflamed, and the corneal surface was completely reepithelialized in 6.0 ± 3.2 (range: 3-10) days in all but one patients. Microperforation occurred in one patient, and a small persistent epithelial defect developed in another. Both were solved uneventfully. In all patients, superficial corneal blood vessels invariably developed, and to further improve vision, conjunctivo-limbal autografting (N ¼ 3) and/or penetrating keratoplasty (N ¼ 3) were performed subsequently. The vision of all patients showed substantial improvement after additional surgeries. Conclusions This study showed the potential of COMET to promote re-epithelialization and reduce inflammation in acute corneal burn, and to reconstruct the corneal surface in chronic burn. COMET may, therefore, be considered an alternative treatment for severe corneal burn.

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Section: Discussionmentioning

confidence: 81%

Transplantation of cultivated oral mucosal epithelial cells for severe corneal burn

Kuo

et al. 2009

Eye

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“…Importantly, our corneal epithelium cell sheets have enhanced optical transparency compared to bioengineered tissues using biologic carriers [17]. Furthermore, only marginal effects on the direct interaction with corneal stroma in the transplanted cell sheets is also one of the merits of our systems, because our previous report suggests that interaction with the host's stromal keratocytes contributes to the maintenance of unique properties of corneal epithelial cells [56]. Therefore, these advantages seem to be essential for the reconstruction of cornea.…”

Section: Resultsmentioning

confidence: 92%

“…Moreover, the substitution of limbal epithelial cells by oral mucosal epithelial cells is also supported by the histological observation that human oral mucosal cell sheets recapitulated a structure comparable to that of the native corneal epithelium [36]. Interestingly, in an animal model of corneal surface reconstruction, follow-ing the transplantation, oral mucosal epithelial cell sheets resembled an expression pattern of keratin similar to that of native corneal epithelial cells rather than native oral mucosal epithelial cells [56]. This phenotypic transformation of oral mucosal epithelial cells on the corneal stroma indicates further that these cells have the potential to be used as an appropriate substitution of limbal epithelial cells, and suggests that the interaction with corneal epithelial cells in the corneal stroma plays a key role in the maintenance of their phenotype.…”

Section: Reconstruction Of the Corneal Epitheliummentioning

confidence: 79%

Regenerative medicine of cornea by cell sheet engineering using temperature-responsive culture surfaces

et al. 2013

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Recently, regenerative medicine has been focused on as next-generation definitive therapies for several diseases or injuries for which there are currently no effective treatments. These therapies have been rapidly developed through the effective fusion between different fields such as stem cell biology and biomaterials. So far, we have proposed "cell sheet engineering" through our core technology that simply applies alterations of the temperature which allows regulation of the attachment or detachment of living cells on the culture surfaces grafted with the temperature-responsive polymer "poly(N-isoproplyacrylamide)". This technology enables us to construct bioengineered sheet-like tissues, termed "cell sheets", without the need of using biodegradable scaffolds and protease treatments that are traditionally used. Therefore, our carrier-free cell sheets not only are independent of the issues observed in conventional methods, but also showed further advantages in the reconstruction of the corneal epithelium or endothelium (e.g. improvement of optical transparency and cell-cell interactions to host stroma in reconstructed tissues). Moreover, our approach does not have issues such as immune rejection or limited number of donors, due to the use of cell sheets derived from autologous limbal (in patients with unilateral disease) or oral mucosal epithelial cells (in patients with bilateral disorders). Indeed, we have successfully performed the clinical application for the reconstruction of ocular surfaces through the transplantation of our carrier-free corneal epithelial cell sheets, as evidenced by improved visual acuity as well as long-term maintenance of postoperative health conditions on ocular surfaces in all patients. We have also proposed a novel approach for the reconstruction of the corneal endothelium using corneal endothelial cell sheets by demonstrating its successful application. Thus, our cell sheet engineering technique provides a breakthrough in the field of regenerative medicine applied to the cornea. cell sheet, temperature-responsive, carrier-free Citation:Umemoto T, Yamato M, Nishida K, et al. Regenerative medicine of cornea by cell sheet engineering using temperature-responsive culture surfaces. Chin Sci Bull, 2013, 58: 43494356,

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“…Next, the TRCD was placed at 20˚C for 60 min. The BMSCs were then separated from the TRCD to be used as a cell sheet (9)(10)(11).…”

Section: Osteoinduction Of Bmscsmentioning

confidence: 99%

Cell sheet-engineered bones used for the reconstruction of mandibular defects in an animal model

Yao

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to investigate the generation of cell sheet-engineered bones used for the reconstruction of mandibular defects. Bone marrow stem cells (BMSCs) were cultured and induced to generate osteoblasts. Poly(lactic-co-glycolic acid) (PLGA) scaffolds were wrapped with or without cell sheets and then implanted into dogs with mandibular defects in the right side (experimental group) or the left side (control group), respectively. Subsequently, X-ray analyses, and hematoxylin and eosin staining were performed at various time points (at 4, 8, 12 or 16 weeks post-implantation; n=4 at each time point). The osteogenesis in the experimental group was significantly improved compared with that in the control group. At 16 weeks after implantation, numerous Haversian systems and a few lamellar bones were observed at the periphery. In the control group, the engineered bone (without BMSC sheets) presented fewer Haversian systems and no lamellar bones. The optical density of the fresh bone in the experimental group was significantly higher compared with that in the control group (P<0.05). In conclusion, tissue-engineered bone with the structure of lamellar bones can be generated using BMSC sheets and implantation of these bones had an improved effects compared with the control group. Cell sheet transplantation was found to enhance bone formation at the reconstruction site of the mandibular defects. IntroductionBone loss is caused by various congenital and degenerative diseases, traumas or incorrect surgical procedures, leading to severe problems, particularly in elderly individuals (1).Tissue engineering is frequently used for the reconstruction of mandible defects. Yamato et al (2) have demonstrated a novel cell sheet engineering method for tissue regeneration, which uses temperature-responsive culture dishes (TRCDs). This technique allows for different types of cultured cells to be noninvasively harvested as intact sheets through simple temperature reduction, without the use of proteolytic enzymes (3). Using this method, the noninvasive transfer of these cell sheets can be achieved, while retaining the typical distributions of Na + /K + -ATPase, glucose transporter-1, sodium-glucose linked transporter-1, aquaporin-1, neutral endopeptidase and dipeptidylendopeptidase IV (4).In the present study, scaffolds of poly(lactic-co-glycolic acid) (PLGA) were produced, and composited with recombination human bone morphogenetic protein-2 (rhBMP-2) and vascular endothelial growth factor (VEGF). In addition, bone marrow stem cells (BMSCs) were cultured in TRCDs to form BMSCs sheets. PLGA/BMP-2/VEGF wrapped with BMSCs sheets were implanted into dogs with mandibular defects. The aim of the present study was to investigate the effects of tissue-engineered bones that have the same structure as normal bones and can be used for the reconstruction of bones with mandible defects. Materials and methodsAnimals. In this study, 16 healthy, adult, male mongrel dogs (age, 14 months; weight, 18-23 kg) were used. All the...

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Ocular Surface Reconstruction Using Autologous Rabbit Oral Mucosal Epithelial Sheets Fabricated Ex Vivo on a Temperature-Responsive Culture Surface

Cited by 122 publications

References 37 publications

Transplantation of cultivated oral mucosal epithelial cells for severe corneal burn

Transplantation of cultivated oral mucosal epithelial cells for severe corneal burn

Regenerative medicine of cornea by cell sheet engineering using temperature-responsive culture surfaces

Cell sheet-engineered bones used for the reconstruction of mandibular defects in an animal model

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