title: A tissue-engineered stomach shows presence of proton pump and G-cells in a rat model, resulting in improved anemia following total gastrectomy.
abstract: Despite advances in surgical reconstruction, total gastrectomy still is accompanied by various complications, especially chronic ones, such as pernicious anemia, resulting in refractory malnutrition. As an alternative approach, we have proposed a tissue-engineered stomach as a replacement of the native stomach. This study aimed to assess the secretory functions of a tissue-engineered stomach in a rat model and the nutritional status of the recipients over an extended time period. Stomach epithelial organoid units were isolated from neonatal rats and seeded onto biodegradable polymers. These constructs were implanted into the omenta of adult recipient rats. After 3 weeks, cyst-like structures had formed, henceforth referred to as tissue-engineered stomachs. The recipient stomachs were resected and replaced by their tissue-engineered counterparts. At 24 weeks after implantation, the secretory function of the tissue-engineered stomach was evaluated using immunohistochemical staining. The hemoglobin levels and nutritional status of the recipients were compared with a control group that had undergone a simple Roux-en-Y reconstruction following total gastrectomy. Recipient rats tolerated the tissue-engineered stomachs well. X-ray examination using barium as contrast showed no bowel stenosis. Staining for proton pump alpha-subunit and gastrin demonstrated the existence of parietal cells and G-cells in the neogastric mucosa, respectively, suggesting secretory functions. The treatment group showed significantly higher hemoglobin levels than the control group, although no differences in the body weight change, total protein, or cholesterol levels were observed between the two groups. A tissue-engineered stomach has the potential to function as a food reservoir following total gastrectomy. It is conjectured that replacement with a tissue-engineered stomach might restore the proton pump parietal cells and G-cells, and thereby improve anemia after a total gastrectomy in a rat model.
authors.affiliation: Division of Traumatology, National Defense Medical College Research Institute, Saitama, and Department of Surgery, National Defense Medical College, Saitama, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Maemura
authors.forename: Michael
authors.initials: M
authors.lastname: Shin
authors.forename: Manabu
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Takashi
authors.initials: T
authors.lastname: Majima
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ishihara
authors.forename: Daizoh
authors.initials: D
authors.lastname: Saitoh
authors.forename: Takashi
authors.initials: T
authors.lastname: Ichikura
mesh_terms: D000713:Anastomosis, Roux-en-Y; D000752:Anemia, Pernicious / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000831:Animals, Newborn; D005743:Gastrectomy / Q000009:adverse effects*; D005753:Gastric Mucosa / Q000201:enzymology / Q000378:metabolism* / Q000601:surgery; D019863:Gastrin-Secreting Cells / Q000201:enzymology / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D023421:Models, Animal; D009940:Organoids / Q000378:metabolism; D010295:Parietal Cells, Gastric / Q000378:metabolism; D017494:Proton Pumps / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D013270:Stomach / Q000201:enzymology / Q000601:surgery; D013997:Time Factors; D046509:Tissue Culture Techniques; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D005755:Gastrins; D006454:Hemoglobins; D017494:Proton Pumps