Evaluation of safety and efficacy of autologous oral mucosa-derived epithelial cell sheet transplantation for prevention of anastomotic restenosis in congenital esophageal atresia and congenital esophageal stenosis.

Background: We performed the first autologous oral mucosa-derived epithelial cell sheet transplantation therapy in a patient with refractory postoperative anastomotic stricture in congenital esophageal atresia (CEA) and confirmed its safety. In this study, patients with CEA and congenital esophageal stenosis were newly added as subjects to further evaluate the safety and efficacy of cell sheet transplantation therapy.

Methods: Epithelial cell sheets were prepared from the oral mucosa of the subjects and transplanted into esophageal tears created by endoscopic balloon dilatation (EBD).

Allogeneic transplantation of epidermal cell sheets followed by endoscopic submucosal dissection to prevent severe esophageal stricture in a porcine model.

Introduction: Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for early esophageal cancer. However, large mucosal defects after esophageal ESD result in refractory strictures. In the present study, we histologically evaluated the endoscopic transplantation of allogeneic epidermal cell sheets (ECSs) as a feasible therapy for preventing esophageal stricture after circumferential ESD in a porcine model.

First-in-human autologous oral mucosal epithelial sheet transplantation to prevent anastomotic re-stenosis in congenital esophageal atresia.

Background: Congenital esophageal atresia postoperative anastomotic stricture occurs in 30-50% of cases. Patients with severe dysphagia are treated with endoscopic balloon dilatation (EBD) and/or local injection of steroids, but many patients continue to experience frequent stricture. In this study, we investigated the transplantation of autologous oral mucosa-derived cell sheets (epithelial cell sheets) as a prophylactic treatment for congenital esophageal atresia postoperative anastomotic stricture.

A stable protocol for the fabrication of transplantable human oral mucosal epithelial cell sheets for clinical application.

Introduction: Cultured stratified epithelial cell sheets have been clinically utilized as transplantable grafts for the regeneration of epithelial tissues, such as the esophagus, cornea, skin, and intraoral cavity. These cell sheets are expected to gain widespread use as regenerative medicine products and save many patients. For this purpose, establishing and disseminating the stale protocol of fabricating the cell sheet is crucial.

Oral keratinocyte-derived exosomes regulate proliferation of fibroblasts and epithelial cells.

Extracellular vesicles (EVs), including exosomes, are small membrane-bound particles released by cells. From a therapeutic point of view, EVs can often convey similar biological function as their parent cell. Grafts originating from oral mucosa have frequently been used in regenerative medicine, and we have previously described the use of oral cell sheets to prevent stricture formation of the esophagus.

Exosomes derived from clinical-grade oral mucosal epithelial cell sheets promote wound healing.

The oral mucosa exhibits unique regenerative properties, sometimes referred to as foetal-like wound healing. Researchers from our institute have used sheets of oral mucosa epithelial cells (OMECs) for regenerative medicine applications including cornea replacement and oesophageal epithelial regeneration for stricture prevention. Here, we have isolated exosomes from clinical-grade production of OMEC sheets from healthy human donors ( = 8), aiming to evaluate the clinical potential of the exosomes to stimulate epithelial regeneration and to improve understanding of the mode-of-action of the cells.

Esophageal tissue engineering: from bench to bedside.

For various esophageal diseases, the search for alternative techniques for tissue repair has led to significant developments in basic and translational research in the field of tissue engineering. Applied to the esophagus, this concept is based on the in vitro combination of elements judged necessary for in vivo implantation to promote esophageal tissue remodeling. Different methods are currently being explored to develop substitutes using cells, scaffolds, or a combination of both, according to the severity of lesions to be treated.

Endoscopic Transplantation of Mesenchymal Stem Cell Sheets in Experimental Colitis in Rats.

Owing to the recent progress in regenerative medicine technology, clinical trials that harnessed the regeneration and immune modulation potentiality of stem cells for treating IBD have shown promising results. We investigated the feasibility and utility of intraluminal endoscopic transplantation of rat MSC sheets in murine models of experimental colitis for targeted delivery of stem cells to lesions. We isolated adipose-derived mesenchymal stem cells (AD-MSC) and bone marrow-derived mesenchymal stem cells (BM-MSC) from EGFP-transgenic rats and fabricated the cells in sheet forms using temperature-responsive culture dishes.

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

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.

Approaches for stricture prevention after esophageal endoscopic resection.

Background And Aims: Endoscopic resection of extensive esophageal lesions has become more common as endoscopic resection techniques and equipment have developed. However, extensive esophageal endoscopic resections can cause postoperative esophageal strictures, which have a negative impact on the quality of life of patients. We aimed to review current treatments and innovative approaches to prevent esophageal strictures after widespread endoscopic resection of esophageal lesions.

Autologous adipose-derived stem cell sheets enhance the strength of intestinal anastomosis.

Objective: Adipose-derived stem cells (ASCs) are capable of multiple differentiation pathways, imparting immunomodulatory effects, and secreting factors that are important for wound healing. These characteristics can be exploited to decrease the incidence of anastomotic leakage.

Methods: In order to delay local wound healing at the anastomotic site, we induced ischemia in a portion of porcine small intestine by ligating vessels.

Transplantation of tissue-engineered cell sheets for stricture prevention after endoscopic submucosal dissection of the oesophagus.

Background And Objective: Endoscopic mucosal dissection (ESD) is a treatment option for oesophagus tumours localized to the mucosa enabling en bloc removal of large lesions. The resulting larger mucosal defects have resulted in an increase in the occurrence of post-treatment strictures. Transplantation of autologous cell sheets, cultured from oral mucosa, has been shown to prevent post-ESD strictures.

Transplantation of epidermal cell sheets by endoscopic balloon dilatation to avoid esophageal re-strictures: initial experience in a porcine model.

Epidermal cell sheet (ECS) transplantation immediately after aggressive endoscopic submucosal dissection (ESD) has been shown to be safe and effective in the prevention of esophageal strictures. This study evaluated the feasibility of ECS transplantation after endoscopic balloon dilation (EBD) in a porcine model. Six pigs underwent circumferential esophageal ESD under general anesthesia.

Treatment of chemically induced oral ulcer using adipose-derived mesenchymal stem cell sheet.

Background: This study investigated the effects of mesenchymal stem cell (MSC) sheet transplantation on healing of chemically induced oral ulceration in a rabbit animal model.

Methods: Oral mucosal ulcers were induced by topical application of filter paper soaked with 70% acetic acid to the anterior gingiva and buccal mucosa of 12 New Zealand white rabbits. The animals were randomly assigned to two groups: with (treatment group, n = 6) or without (control group, n = 6) cell sheets applied to ulcers.

Report of the International Regulatory Forum on Human Cell Therapy and Gene Therapy Products.

The development of human cell therapy and gene therapy products has progressed internationally. Efforts have been made to address regulatory challenges in the evaluation of quality, efficacy, and safety of the products. In this forum, updates on the specific challenges in quality, efficacy, and safety of products in the view of international development were shared through the exchange of information and opinions among experts from regulatory authorities, academic institutions, and industry practitioners.

Novel isolated cecal pouch model for endoscopic observation in rats.

Aim: To create a new rat model for drug administration, cell transplantation, and endoscopic examination for the treatment of intestinal diseases.

Methods: F344/NJc l-rnu/rnu rats (10-wk-old males, 350-400 g) were used in this study. The rats were anesthetized via 2% isoflurane inhalation.

Endoscopic cell sheet transplantation device developed by using a 3-dimensional printer and its feasibility evaluation in a porcine model.

Background: To prevent severe esophageal stenosis after aggressive endoscopic submucosal dissection (ESD), our group previously reported an efficient treatment using cell sheets that had been fabricated from patient cells. However, this transplantation procedure had not been easy for every endoscopist and needed to be improved to derive the full effect of epithelial cell sheets.

Objective: To develop an endoscopic device that enables easy and effective cell sheet transplantation and to evaluate its performance and clinical feasibility.

How to prevent contamination with during the fabrication of transplantable oral mucosal epithelial cell sheets.

We have utilized patients' own oral mucosa as a cell source for the fabrication of transplantable epithelial cell sheets to treat limbal stem cell deficiency and mucosal defects after endoscopic submucosal dissection of esophageal cancer. Because there are abundant microbiotas in the human oral cavity, the oral mucosa was sterilized and 40 μg/mL gentamicin and 0.27 μg/mL amphotericin B were added to the culture medium in our protocol.

Prevention of esophageal strictures after endoscopic submucosal dissection.

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have recently been accepted as less invasive methods for treating patients with early esophageal cancers such as squamous cell carcinoma and dysplasia of Barrett's esophagus. However, the large defects in the esophageal mucosa often cause severe esophageal strictures, which dramatically reduce the patient's quality of life. Although preventive endoscopic balloon dilatation can reduce dysphagia and the frequency of dilatation, other approaches are necessary to prevent esophageal strictures after ESD.

Cell sheets engineering for esophageal regenerative medicine.

Recently, cell-based therapies, regenerative medicine, and tissue engineering have been progressing rapidly. We have developed a novel strategy for regenerative medicine to recover tissue functions using temperature-responsive cell culture surfaces. To overcome of conventional methods such as the usage of single-cell suspension injection, we have applied transplantable cell sheets fabricated with temperature-responsive culture surfaces for cell delivery.

Application of regenerative medical technology using tissue-engineered cell sheets for endoscopic submucosal dissection of esophageal neoplasms.

We have developed a technique for endoscopic transplantation of cultured autologous oral mucosal epithelial cell sheets to an esophageal ulcer following endoscopic submucosal dissection (ESD). The epithelial cell sheets successfully prevented esophageal stricture after ESD. Key technology is that epithelial cell sheets cultured from oral mucosal tissue and attached proteins can be harvested using cell sheet technology and can be transplanted to a wound site without the use of adhesive material.

Cell sheet technology for regeneration of esophageal mucosa.

The progress of tissue-engineering technology has realized development of new therapies to treat various disorders by using cultured cells. Cell- and tissue-based therapies have been successfully applied to human patients, and several tissue-engineered products have been approved by the regulatory agencies and are commercially available. In the review article, we describe our experience of development and clinical application of cell sheet-based regenerative medicine.

[Regenerative medicine using cell-sheet engineering].

We have developed a novel strategy for regenerative medicine to recover tissue functions using temperature-responsive cell culture surfaces. To overcome the disadvantages of conventional methods such as the usage of single-cell suspension injections and biodegradable polymer scaffolds, we use transplantable cell sheets fabricated with temperature-responsive culture surfaces for cell delivery. Here, we summarize our progress in promoting regenerative medicine using cell-sheet engineering with respect to research and regulatory systems and describe recent challenges in the standardization of cell-sheet engineering.