Gupta Ashish, Dixit Anupam, Sales Kevin M, Winslet Marc C, Seifalian Alexander M
Biomaterials and Tissue Engineering Centre, Academic Division of Surgery and Interventional Sciences, University College London, London NW3 2PF, United Kingdom.
Biomacromolecules. 2006 Oct;7(10):2701-9. doi: 10.1021/bm060383e.
Short bowel syndrome (SBS) has always posed a great threat to patients and has been one of the biggest challenges for doctors due to its high morbidity and mortality. So far, parenteral nutrition (PN) and small bowel transplantation remain the only viable therapeutic options. However, sepsis and liver failure associated with PN and limited availability of the donor organs and high graft rejection rates associated with transplantation have limited their use to a nonpermanent solution. Clearly, there is a need for an alternative therapy whereby increasing the absorptive surface area would help neonates and adults suffering from permanent intestinal failure. Techniques such as sequential intestinal lengthening are being explored in animal models with little success. Attempts to engineer small intestine since the late 1980s have achieved varying degrees of success in animal models with evolving refinements in biotechnology. The most encouraging results so far have been the generation of intestinal neomucosa in the form of cysts when intestinal epithelial organoid units isolated from neonatal rats were seeded onto biodegradable polymers before implantation in syngeneic adult rats' omentum. Although still experimental, continued attempts worldwide using cultured stem cells and improved polymer technology offer promise to provide an off-the-shelf artificial intestine as a novel therapy for patients with SBS. This article reviews the current status of progress in the field of small intestinal tissue engineering and addresses various types of cell sources and scaffold material having potential to be used in this field.
短肠综合征(SBS)一直对患者构成巨大威胁,因其高发病率和死亡率,一直是医生面临的最大挑战之一。到目前为止,肠外营养(PN)和小肠移植仍然是仅有的可行治疗选择。然而,与PN相关的败血症和肝功能衰竭,以及供体器官供应有限和与移植相关的高移植排斥率,限制了它们仅作为一种非永久性解决方案的应用。显然,需要一种替代疗法,增加吸收表面积将有助于患有永久性肠衰竭的新生儿和成年人。诸如序贯小肠延长等技术正在动物模型中进行探索,但收效甚微。自20世纪80年代末以来,在动物模型中尝试构建小肠,随着生物技术的不断改进取得了不同程度的成功。迄今为止,最令人鼓舞的结果是,当从新生大鼠分离的肠上皮类器官单元接种到可生物降解聚合物上,然后植入同基因成年大鼠的网膜时,会以囊肿的形式产生肠新黏膜。尽管仍处于实验阶段,但全球范围内持续尝试使用培养的干细胞和改进的聚合物技术有望提供一种现成的人工小肠,作为SBS患者的一种新疗法。本文综述了小肠组织工程领域的当前进展状况,并探讨了该领域可能使用的各种细胞来源和支架材料。