Transplanting Engineered Mucosal Tissue into the Esophagus

Researchers have engineered tissues from oral epithelial cells that can be transplanted into the esophagus and promote healing after tumors are removed.

According to the September issue of Gastroenterology, sutureless, endoscopic transplantation of sheets of autologous oral mucosal epithelial cells safely and effectively promotes re-epithelialization of the esophagus after surgery.

Superficial esophageal neoplasms are often removed by esophageal endoscopic submucosal dissection (ESD). However, this leaves an ulcer that takes 4 weeks or more to heal, and many patients develop esophageal strictures (narrowing or tightening of the esophagus). The strictures cause dysphagia and can require balloon dilation.

Ohki et al. collected interior buccal mucosal tissue (approximately 6 mm in diameter per cell sheet) from 9 patients with superficial esophageal neoplasms. The epithelial cells were isolated and then cultured for 16 days. Sheets of mucosal epithelial cells (23 mm in diameter) were then collected and transferred, using endoscopic forceps, onto the esophageal ulcer, immediately after ESD (see video).

The procedure of esophageal ESD and endoscopic cell sheet transplantation. Cell sheets were transplanted to the site of ulceration using endoscopic forceps and a support membrane. After a 10-minute wait, the deposit of extracellular matrix underneath the cell sheets allowed the rapid adhesion to the ulcer surface without sutures.

The authors observed complete re-epithelialization within a median time of 3.5 weeks—similar to the normal healing time. However, no patients developed dysphagia, strictures, or other complications following the ESD, except for 1 patient who had a full circumferential ulceration that expanded to the esophagogastric junction.

Ohki et al. conclude that sheets of engineered epithelial cells, fabricated ex vivo from autologous oral mucosal epithelium, effectively reconstruct the esophageal luminal surface and prevent stricture in patients following esophageal ESD.

They propose that the transplanted cells could serve as the source of the regenerated epithelia, because transplanted epithelial cells were detected in biopsy samples of the healed tissue. However, growth factors and cytokines secreted by transplanted cell sheets are also likely to promote wound healing.

In an editorial that accompanies the article, Joshua D. Penfield et al. explain that  autologous epithelial cell sheet transplantation is already being used in the field of burn surgery, and that rapid epithelialization can prevent scarring and contraction of the mucosa. They propose several mechanisms that could facilitate rapid epithelialization of the mucosa, including interactions with mesenchymal cells and secretion of cytokines and other growth factors from the transplanted cell sheets.

Long-term studies with more patients are needed to further assess the benefits and risks of this method. Ohki et al. propose that this technique might be developed to treat patients with larger esophageal tumors, or neoplasms that arise in patients with Barrett’s esophagus.

Read the article online.
Ohki T, Yamato M, Ota M, et al. Prevention of esophageal stricture after endoscopic submucosal dissection using tissue-engineered cell sheets. Gastroenterology 2012;143: 582−588.e2.

Read the accompanying editorial.
Penfield JD, Gorospe EC, Wang KK. Tissue-engineered cell sheets for stricture prevention: a new connection between endoscopy and regenerative medicine. Gastroenterology 2012;143:526−529.

About Kristine Novak, PhD, Science Editor

Dr. Kristine Novak is the science editor for Gastroenterology and Clinical Gastroenterology and Hepatology, both published by the American Gastroenterological Association. She has worked as an editor at biomedical research journals and as a science writer for more than 12 years, covering advances in gastroenterology, hepatology, cancer, immunology, biotechnology, molecular genetics, and clinical trials. She has a PhD in cell biology and an interest in all areas of medical research.
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