Belchior Gustavo Gross, Sogayar Mari Cleide, Grikscheit Tracy Cannon
Biochemistry Department, Chemistry Institute, University of São Paulo, Brazil.
Biochemistry Department, Chemistry Institute, University of São Paulo, Brazil; Cell and Molecular Therapy Center (NUCEL/NETCEM), School of Medicine, University of São Paulo, Brazil.
Semin Pediatr Surg. 2014 Jun;23(3):141-9. doi: 10.1053/j.sempedsurg.2014.06.011. Epub 2014 Jun 4.
Tissue engineering currently constitutes a complex, multidisciplinary field exploring ideal sources of cells in combination with scaffolds or delivery systems in order to form a new, functional organ to replace native organ lack or loss. Short bowel syndrome (SBS) is a life-threatening condition with high morbidity and mortality rates in children. Current therapeutic strategies consist of costly and risky allotransplants that demand lifelong immunosuppression. A promising alternative is the implantation of autologous organoid units (OU) to create a tissue-engineered small intestine (TESI). This strategy is proven to be stem cell and mesenchyme dependent. Intestinal stem cells (ISCs) are located at the base of the crypt and are responsible for repopulating the cycling mucosa up to the villus tip. The stem cell niche governs the biology of ISCs and, together with the rest of the epithelium, communicates with the underlying mesenchyme to sustain intestinal homeostasis. Biopharmaceuticals are broadly used in the clinic to activate or enhance known signaling pathways and may greatly contribute to the development of a full-thickness intestine by increasing mucosal surface area, improving blood supply, and determining stem cell fate. This review will focus on tissue engineering as a means of building the new small intestine, highlighting the importance of stem cells and recombinant peptide growth factors as biopharmaceuticals.
组织工程学目前是一个复杂的多学科领域，它探索理想的细胞来源，并与支架或递送系统相结合，以形成一个新的功能性器官，来替代天然器官的缺失或丧失。短肠综合征（SBS）是一种危及生命的疾病，在儿童中发病率和死亡率都很高。目前的治疗策略包括昂贵且有风险的同种异体移植，这种移植需要终身免疫抑制。一个有前景的替代方案是植入自体类器官单元（OU）来构建组织工程化小肠（TESI）。这一策略已被证明依赖于干细胞和间充质。肠干细胞（ISC）位于隐窝底部，负责使循环的黏膜重新增殖直至绒毛顶端。干细胞微环境控制着ISC的生物学特性，并与上皮的其他部分一起与下方的间充质进行沟通，以维持肠道内环境稳定。生物制药在临床上被广泛用于激活或增强已知的信号通路，并且通过增加黏膜表面积、改善血液供应以及决定干细胞命运，可能对全层小肠的发育有很大贡献。本综述将聚焦于作为构建新小肠手段的组织工程学，强调干细胞和重组肽生长因子作为生物制药的重要性。
