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 epid...

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Main Authors: Shinichiro Kobayashi, Nobuo Kanai, Masayuki Yamato, Susumu Eguchi
Format: Article
Language:English
Published: Elsevier 2022-12-01
Series:Regenerative Therapy
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S235232042200061X
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author Shinichiro Kobayashi
Nobuo Kanai
Masayuki Yamato
Susumu Eguchi
author_facet Shinichiro Kobayashi
Nobuo Kanai
Masayuki Yamato
Susumu Eguchi
author_sort Shinichiro Kobayashi
collection DOAJ
description 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. Methods: Epidermal cells were isolated from the skin tissue of allogeneic pigs and cultured on temperature-responsive cell culture inserts for 2 weeks. Transplantable ECSs were harvested by reducing the temperature and endoscopically transplanting the sheets to ulcer sites immediately after esophageal ESD. The engraftment of transplanted ECSs was then evaluated in two pigs at 7 days after transplantation. Next, ten pigs were divided into two groups to evaluate the endoscopic transplantation of allogeneic ECSs for the prevention of esophageal strictures after ESD. Allogeneic ECSs were transplanted immediately after esophageal ESD in the transplantation group (n = 5), whereas the control group (n = 5) did not undergo transplantation. Results: Most of the transplanted allogeneic ECSs were successfully engrafted at the ulcer sites in the early phase. Fluorescence in situ hybridization analysis revealed that several allogeneic cells were present in the transplanted area at 7 days after ESD. At 14 days after ESD, significant differences in body weight loss, dysphagia scores, and mucosal strictures were observed between the control and transplantation groups. Transplanting allogeneic ECSs after esophageal ESD promotes mucosal healing and angiogenesis and prevents excessive inflammation and granulation tissue formation. Conclusions: Endoscopic and histological analyses revealed that allogeneic ECSs promoted artificial ulcer healing after ESD, preventing esophageal strictures after ESD.
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spelling doaj.art-a9a6cab5592145e09af58a5416bbcf442022-12-22T03:51:53ZengElsevierRegenerative Therapy2352-32042022-12-0121157165Allogeneic transplantation of epidermal cell sheets followed by endoscopic submucosal dissection to prevent severe esophageal stricture in a porcine modelShinichiro Kobayashi0Nobuo Kanai1Masayuki Yamato2Susumu Eguchi3Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Institute of Advanced Biomedical Engineering and Science (TWIns), Tokyo Women's Medical University, Tokyo, JapanInstitute of Advanced Biomedical Engineering and Science (TWIns), Tokyo Women's Medical University, Tokyo, Japan; Health Aging Innovation Center, Tokyo Metropolitan Geriatric Medical Center, Tokyo, JapanInstitute of Advanced Biomedical Engineering and Science (TWIns), Tokyo Women's Medical University, Tokyo, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Corresponding author. Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, Nagasaki, 8528102, Japan. Fax: +81-95-819-7319Introduction: 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. Methods: Epidermal cells were isolated from the skin tissue of allogeneic pigs and cultured on temperature-responsive cell culture inserts for 2 weeks. Transplantable ECSs were harvested by reducing the temperature and endoscopically transplanting the sheets to ulcer sites immediately after esophageal ESD. The engraftment of transplanted ECSs was then evaluated in two pigs at 7 days after transplantation. Next, ten pigs were divided into two groups to evaluate the endoscopic transplantation of allogeneic ECSs for the prevention of esophageal strictures after ESD. Allogeneic ECSs were transplanted immediately after esophageal ESD in the transplantation group (n = 5), whereas the control group (n = 5) did not undergo transplantation. Results: Most of the transplanted allogeneic ECSs were successfully engrafted at the ulcer sites in the early phase. Fluorescence in situ hybridization analysis revealed that several allogeneic cells were present in the transplanted area at 7 days after ESD. At 14 days after ESD, significant differences in body weight loss, dysphagia scores, and mucosal strictures were observed between the control and transplantation groups. Transplanting allogeneic ECSs after esophageal ESD promotes mucosal healing and angiogenesis and prevents excessive inflammation and granulation tissue formation. Conclusions: Endoscopic and histological analyses revealed that allogeneic ECSs promoted artificial ulcer healing after ESD, preventing esophageal strictures after ESD.http://www.sciencedirect.com/science/article/pii/S235232042200061XEsophageal stricturesWound healingAngiogenesisAllogeneic transplantationEpithelial-to-mesenchymal transition
spellingShingle Shinichiro Kobayashi
Nobuo Kanai
Masayuki Yamato
Susumu Eguchi
Allogeneic transplantation of epidermal cell sheets followed by endoscopic submucosal dissection to prevent severe esophageal stricture in a porcine model
Regenerative Therapy
Esophageal strictures
Wound healing
Angiogenesis
Allogeneic transplantation
Epithelial-to-mesenchymal transition
title Allogeneic transplantation of epidermal cell sheets followed by endoscopic submucosal dissection to prevent severe esophageal stricture in a porcine model
title_full Allogeneic transplantation of epidermal cell sheets followed by endoscopic submucosal dissection to prevent severe esophageal stricture in a porcine model
title_fullStr Allogeneic transplantation of epidermal cell sheets followed by endoscopic submucosal dissection to prevent severe esophageal stricture in a porcine model
title_full_unstemmed Allogeneic transplantation of epidermal cell sheets followed by endoscopic submucosal dissection to prevent severe esophageal stricture in a porcine model
title_short Allogeneic transplantation of epidermal cell sheets followed by endoscopic submucosal dissection to prevent severe esophageal stricture in a porcine model
title_sort allogeneic transplantation of epidermal cell sheets followed by endoscopic submucosal dissection to prevent severe esophageal stricture in a porcine model
topic Esophageal strictures
Wound healing
Angiogenesis
Allogeneic transplantation
Epithelial-to-mesenchymal transition
url http://www.sciencedirect.com/science/article/pii/S235232042200061X
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