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Tissue Fabrication and Regeneration by Cell Sheet Technology
Published in Gilson Khang, Handbook of Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine, 2017
Yuji Haraguchi, Tatsuya Shimizu, Masayuki Yamato, Teruo Okano
Clinical therapy using cell sheet technology is performed in the field of ophthalmology.97 Limbal stem cell deficiency from severe trauma by thermal or chemical burns or some diseases such as Stevens–Johnson syndrome or ocular pemphigoid can result in corneal opacification with severe visual loss. Although corneal transplantation therapy with donated corneas is usually performed, there is a high risk of graft rejection and a chronic donor shortage. A cell sheet therapy with autologous oral mucosal epithelium has been performed to improve the visual acuity of patients with complete bilateral corneal epithelial stem cell deficiencies.98 Maintaining both cell–cell junctions and deposited ECM on the basal surface, the cell sheets can adhere onto the corneal surfaces of the host eyes without suturing, and the surfaces are confirmed to be completely protected from fluorescein penetration immediately after the transplantation.24,97,98 The first clinical study has shown good outcomes with the long-term maintenance of healthy ocular surfaces with significant recoveries in all (four) patients who had lost their vision. On the basis of encouraging results, in France, a clinical study has been also performed.99 In the study, 25 patients (26 eyes) received autologous oral mucosal epithelial cell sheets. The result of the clinical therapy shows that the oral mucosal epithelial cell sheet is a well-tolerated and safe tissue-engineered product. These results confirm the efficacy of cell sheets for reconstructing the ocular surface in patients with total bilateral corneal limbal epithelial stem cell deficiency.
Eye tissue regeneration and engineering
Published in David M. Gardiner, Regenerative Engineering and Developmental Biology, 2017
Konstantinos Sousounis, Joelle Baddour, Panagiotis A. Tsonis *
Cells in contact with the external environment are part of the corneal epithelium. The epithelium’s main function is to keep the structural integrity of the cornea and protect it from particles and pathogens (Notara et al. 2010). Corneal epithelial cells exhibit some proliferation capabilities, but they are also dependent on their progenitors at the limbus to maintain homeostasis (Dua et al. 2009; Majo et al. 2008; Li et al. 2007). The limbus is the area where cornea and sclera connect. It has been shown that this progenitor cell population plays an important role in keeping non-transparent epithelial cells of the sclera from invading the cornea and causing blurriness. The same holds true for other tissues found in the sclera, such as blood vessels (Osei-Bempong et al. 2013). Diseases associated with the corneal epithelium are also directly related with the stem cells found at the limbus. After damage (e.g., burn injury), limbal stem cells might become reduced in number, allowing epithelial cells from the sclera to invade and cover the pupil in patients, leading to a progressive reduction in visual acuity (Osei-Bempong et al. 2013). Penetrating keratoplasty, a common transplantation method used to treat corneal endothelium–associated diseases, does not replace the number of limbal stem cells and, as such, is ineffective. Current methods to treat limbal stem cell deficiency depend on ex vivo expansion of an autologous limbal stem cell population followed by transplantation of these cells in the eye, a method called cultivated limbal epithelial transplantation (CLET) (Rama et al. 2010* ; Pellegrini et al. 1997). When the limbus is severely damaged and biopsy cannot be performed, a method known as cultivated oral mucosa epithelium transplantation (COMET) has been successfully used to restore corneal epithelium homeostasis (Nishida et al. 2004).
Future potential of engineered heart tissue patches for repairing the damage caused by heart attacks
Published in Expert Review of Medical Devices, 2020
Richard J. Jabbour, Thomas J. Owen, Pragati Pandey, Sian E. Harding
However, this route is time-consuming, expensive and more complex than previously thought with cells taken from diseased donors often expressing phenotypes of the disease. These reasons are why in part the first clinical studies have utilized an allogenic approach. Menasché et al. reported a phase I feasibility in which cardiovascular progenitors were seeded onto a fibrin-based patch in patient undergoing coronary artery bypass grafting [7]. Cells were from an allogenic cell source and all patents received immunosuppression for a period of 1 month. Feasibility was shown in this 6-patient trial. A similar trial has recently been granted approval in Japan using cell sheet technology and plans to use 100 million cells again from an allogenic cell source. These trials are primarily studying safety including the incidence of arrhythmias. There may be several reasons for an allogenic approach over autologous, including the possibility of extensive preclinical testing of a specific cell line to ensure viability and effectiveness, and the potential for an off the shelf product and more viable business model. For example, autologous approaches of other organ systems are limited but autologous human corneal epithelial cells (Holoclar) cost £80,000 per eye (NHS list price) when used to treat advanced limbal stem cell deficiency after eye burns.