Maemura Tomoyuki, Shin Michael, Kinoshita Manabu, Majima Takashi, Ishihara Masayuki, Saitoh Daizoh, Ichikura Takashi
Division of Traumatology, National Defense Medical College Research Institute, Saitama, and Department of Surgery, National Defense Medical College, Saitama, Japan.
Artif Organs. 2008 Mar;32(3):234-9. doi: 10.1111/j.1525-1594.2007.00528.x. Epub 2008 Jan 15.
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.
尽管手术重建技术取得了进展,但全胃切除术仍伴随着各种并发症,尤其是慢性并发症,如恶性贫血,导致难治性营养不良。作为一种替代方法,我们提出了用组织工程胃替代天然胃。本研究旨在评估大鼠模型中组织工程胃的分泌功能以及受体在较长时间段内的营养状况。从新生大鼠中分离出胃上皮类器官单位,并接种到可生物降解的聚合物上。将这些构建体植入成年受体大鼠的网膜中。3周后,形成了囊状结构,此后称为组织工程胃。切除受体的胃,并用组织工程胃替代。植入后24周,使用免疫组织化学染色评估组织工程胃的分泌功能。将受体的血红蛋白水平和营养状况与全胃切除术后接受简单Roux-en-Y重建的对照组进行比较。受体大鼠对组织工程胃耐受良好。使用钡剂作为造影剂的X线检查未显示肠道狭窄。质子泵α亚基和胃泌素染色分别显示新胃黏膜中存在壁细胞和G细胞,提示有分泌功能。治疗组的血红蛋白水平明显高于对照组,尽管两组之间在体重变化、总蛋白或胆固醇水平方面未观察到差异。组织工程胃有可能在全胃切除术后起到食物储存器的作用。据推测,用组织工程胃替代可能会恢复质子泵壁细胞和G细胞,从而改善大鼠模型全胃切除术后的贫血状况。