Oral epithelial cell sheets engraftment for esophageal strictures after endoscopic submucosal dissection of squamous cell carcinoma and airplane transportation

Abstract

Endoscopic submucosal dissection (ESD) permits en bloc removal of superficial oesophageal squamous cell carcinoma (ESCC). However, post-procedure stricture is common after ESD for widespread tumours, and multiple endoscopic balloon dilation (EBD) procedures are required. We aimed to evaluate the safety and effectiveness of endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets that had been transported by air over a distance of 1200 km in controlling postprocedural oesophageal stricture. Ten patients who underwent complete circular or semicircular ESD for ESCC were transplanted with cell sheets. The safety of the entire process including cell sheet preparation, transport, ESD and cell sheet transplantation was assessed. The incidence of oesophageal stricture, number of EBD sessions, and time until epithelialization were investigated. Each ESD was successfully performed, with subsequent cell sheet engrafting carried out safely. Following cell sheet transplantation, the luminal stenosis rate was 40%, while the median number of EBD sessions was 0. The median post-ESD ulcer healing period was rather short at 36 days. There were no significant complications at any stage of the process. Cell sheet transplantation and preparation at distant sites and transportation by air could be a safe and promising regenerative medicine technology.

Cell sheet tissue engineering: Cell sheet preparation, harvesting/manipulation, and transplantation

“…Ten patients have been treated at Tokyo Women's Medical University. In addition, collaborative clinical studies have been conducted for the treatment of 10 patients at Nagasaki University Hospital 18 and for 10 patients suffering from Barrett's esophagus at Karolinska Institute in Sweden. 69 Periodontal ligament (PL) cells from wisdom teeth were utilized for making PL cell sheet to treat periodontitis patients.…”

“…1). Cell sheet tissue engineering has reported first-in-human clinical use in seven fields including heart, 13,14 cornea, 15,16 esophagus, 17,18 periodontal, 19,20 middle chamber of ear, 21 knee cartilage, 22 and lung. 23 The expectations for cell therapy in disease and tissueinjury management are disproportionate to the successes manifested.…”

Decellularized human corneal stromal cell sheet as a novel matrix for ocular surface reconstruction

“…For example, an autologous myoblast sheet which was generated from skeletal muscle was used and transplanted to the lateral surface of the dilated heart of a patient suffering from dilated cardiomyopathy (DCM;Sawa et al, 2015). It was also used to reconstruct defects of the esophagus (Yamaguchi et al, 2017), middle cavity of the ear (Yamamoto et al, 2017), lung (Kanzaki, Takagi, Washio, Kokubo, & Yamato, 2017), periodontal tissue (Iwata et al, 2018), and the cornea (Nishida et al, 2004). For the cornea, this method has mostly been used for corneal epithelial cell and limbal epithelial stem cell transplantation in patients with unilateral stem cell deficiency (Umemoto, Yamato, Nishida, & Okano, 2013).…”

Stable cell adhesion affects mesenchymal stem cell sheet fabrication: Effects of fetal bovine serum and human platelet lysate

“…Retained native endogenous cell adhesion proteins provide several strategic advantages for cell sheet engraftment and retention at target tissues. Over 15 years of clinical data support enhanced therapeutic properties for autologous‐sourced cell sheets through increased cell retention at target tissues (Ebihara et al, 2012; Iwata et al, 2018; Kanzaki, Takagi, Washio, Kokubo, & Yamato, 2017; Nishida et al, 2004; Ohki et al, 2012; Sawa et al, 2015; Yamaguchi et al, 2017; Yamamoto et al, 2017). Recently, several preclinical studies have also reported MSC sheet use in wound healing, heart, and pancreas regeneration (Kato et al, 2015; Kim et al, 2018; Miyahara et al, 2006).…”