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摘要 : 科学家在《自然-医学》杂志上发表报告称,他们能够用人体干细胞培育出功能性人体肠道组织并将其移植入小鼠体内。这种人鼠肠道组织模型或可用于研究发育过程、肠胃疾病以及测试针对特定病症的新治疗方法。




Michael Helmrath等人发现,如果将这种实验室生长的组织移植入小鼠的肾脏组织,其比在实验室中培养发育要成熟得多,而且最终能够发育成与人体小肠类似的复杂结构。从解剖学角度来看,该组织发育出了小肠的特征结构包括隐窝和绒毛等,还有一些不同类型的肠道细胞。这种组织还展现出了消化功能,比如将分子吸收输送到小鼠的血液中以及消化酶活动。研究人员还发现如果将小鼠的一部分肠道通过手术移除,会促进植入的人体组织的生长和兼容,这意味着人体肠道组织可对小鼠体内血液循环释放的信号产生反应。


An in vivo model of human small intestine using pluripotent stem cells


Differentiation of human pluripotent stem cells (hPSCs) into organ-specific subtypes offers an exciting avenue for the study of embryonic development and disease processes, for pharmacologic studies and as a potential resource for therapeutic transplant1, 2. To date, limited in vivo models exist for human intestine, all of which are dependent upon primary epithelial cultures or digested tissue from surgical biopsies that include mesenchymal cells transplanted on biodegradable scaffolds3, 4. Here, we generated human intestinal organoids (HIOs) produced in vitro from human embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs)5, 6 that can engraft in vivo. These HIOs form mature human intestinal epithelium with intestinal stem cells contributing to the crypt-villus architecture and a laminated human mesenchyme, both supported by mouse vasculature ingrowth. In vivo transplantation resulted in marked expansion and maturation of the epithelium and mesenchyme, as demonstrated by differentiated intestinal cell lineages (enterocytes, goblet cells, Paneth cells, tuft cells and enteroendocrine cells), presence of functional brush-border enzymes (lactase, sucrase-isomaltase and dipeptidyl peptidase 4) and visible subepithelial and smooth muscle layers when compared with HIOs in vitro. Transplanted intestinal tissues demonstrated digestive functions as shown by permeability and peptide uptake studies. Furthermore, transplanted HIO-derived tissue was responsive to systemic signals from the host mouse following ileocecal resection, suggesting a role for circulating factors in the intestinal adaptive response7, 8, 9. This model of the human small intestine may pave the way for studies of intestinal physiology, disease and translational studies.


来源: Nature Medicine 浏览次数:68


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