Perez Alexander, Grikscheit Tracy C, Blumberg Richard S, Ashley Stanley W, Vacanti Joseph P, Whang Edward E
Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
Transplantation. 2002 Sep 15;74(5):619-23. doi: 10.1097/00007890-200209150-00006.
Using tissue-engineering techniques, we have developed a that regenerates structural and transporter properties of native jejunum. The purpose of this study was to characterize the mucosal immune system of the engineered neointestine. We hypothesized that the neointestinal mucosa is capable of developing a mature immunocyte population and that exposure to luminal stimuli is critical to this development.
Neointestinal cysts were engineered by implanting polymer-organoid constructs into syngeneic adult recipients. Neointestine (cysts left nonanastomosed [NA] and cysts anastomosed to native bowel [AN]) and native jejunum were harvested serially (3-56 weeks postoperatively). Immune cell subsets were characterized by the immunohistochemical detection of cell-specific antigens (T cells [CD3], B cells [CD32], NK cells [CD56], and macrophages [CD68]) combined with computer-based morphometry.
Intraepithelial and lamina propria immunocyte population densities and subset distributions were identical in AN cysts harvested 20 weeks postoperatively and in native jejunum. Mucosal immunocyte population densities were lower in AN cysts harvested 10 weeks postoperatively and only rudimentary in NA cysts, even those harvested 20 weeks postoperatively.
These results suggest that tissue-engineered intestine has the capacity to develop a mucosal immune system with an immunocyte population similar to that of native small intestine. The development of this immune system is a function of both exposure to luminal stimuli and the duration of this exposure. Tissue-engineered intestine offers promise as a new therapeutic approach for patients who have intestinal insufficiency.
利用组织工程技术，我们构建了一种能再生天然空肠结构和转运特性的组织工程空肠。本研究旨在对工程化新肠的黏膜免疫系统进行特征描述。我们假设新肠黏膜能够发育出成熟的免疫细胞群体，并且暴露于肠腔刺激对这一发育过程至关重要。
通过将聚合物 - 类器官构建体植入同基因成年受体来构建新肠囊肿。连续获取新肠（未吻合的囊肿[NA]和与天然肠吻合的囊肿[AN]）以及天然空肠（术后3 - 56周）。通过免疫组织化学检测细胞特异性抗原（T细胞[CD3]、B细胞[CD32]、NK细胞[CD56]和巨噬细胞[CD68]）并结合计算机形态测量法来对免疫细胞亚群进行特征描述。
术后20周获取的AN囊肿中上皮内和固有层免疫细胞群体密度及亚群分布与天然空肠相同。术后10周获取的AN囊肿中黏膜免疫细胞群体密度较低，而NA囊肿中即使是术后20周获取的也仅有初步发育。
这些结果表明，组织工程化肠道有能力发育出与天然小肠相似的具有免疫细胞群体的黏膜免疫系统。这种免疫系统的发育是暴露于肠腔刺激及其持续时间的函数。组织工程化肠道有望成为治疗肠道功能不全患者的一种新的治疗方法。
