Hohwieler M, Renz S, Liebau S, Lin Q, Lechel A, Klaus J, Perkhofer L, Zenke M, Seufferlein T, Illing A, Müller M, Kleger A
Institute of Neuroanatomy, Eberhard Karls University Tuebingen, Germany.
Department of Cell Biology, Institute for Biomedical Engineering, Medical Faculty, RWTH University Aachen, Germany.
Z Gastroenterol. 2016 Aug;54(8):748-59. doi: 10.1055/s-0042-105520. Epub 2016 Jul 14.
Human pluripotent stem cells represent a powerful tool to study human embryonic development and disease but also open up novel strategies for cell replacement therapies. Their capacity to give rise to every cell type of the human body, meanwhile, enables researchers to generate high yields of mesodermal, ectodermal, but also endodermal-derived tissues such as hepatic, pancreatic, or intestinal cells. Another progress in the field came with the advent of 3-dimensional culture conditions, so-called organoids, which facilitate maturation of stem cells and in turn more faithfully recapitulate human tissue architecture. While several studies reported the derivation of organoid cultures from adult intestinal tissue, the derivation of intestinal organoids derived from plucked human hair of Crohn's disease patients has not been reported. The current research project reports such successful generation and characterization of induced pluripotent stem cells (iPSCs) derived from hair sheet keratinocyte cultures of a patient with Crohn's disease. Stepwise differentiation along the intestinal lineage showed no differences in intermediate stages such as definitive endoderm formation. We also directed the patterned primitive gut tube toward intestinal organoids resembling the cellular architecture of human "miniguts". As expected from current pathophysiological knowledge on Crohn's disease, there were no obvious morphological differences in the "miniguts" derived from healthy control and diseased patient-induced pluripotent stem cells. Taken together, our platform will enable for detailed and complementary phenotyping of the pathophysiology of Crohn's disease in a novel disease-in-a-dish format.
人类多能干细胞是研究人类胚胎发育和疾病的有力工具，同时也为细胞替代疗法开辟了新策略。与此同时，它们分化成人体各种细胞类型的能力使研究人员能够大量生成中胚层、外胚层以及内胚层来源的组织，如肝脏、胰腺或肠道细胞。该领域的另一项进展是三维培养条件的出现，即所谓的类器官，它促进了干细胞的成熟，进而更忠实地再现人体组织结构。虽然有几项研究报道了从成人肠道组织中获得类器官培养物，但尚未有从克罗恩病患者拔下的头发中获得肠道类器官的报道。当前的研究项目报告了从一名克罗恩病患者的毛囊角质形成细胞培养物中成功生成并鉴定诱导多能干细胞（iPSC）的情况。沿着肠道谱系的逐步分化在中间阶段，如确定内胚层形成方面没有差异。我们还将模式化的原始肠管诱导分化为类似人类“迷你肠道”细胞结构的肠道类器官。正如目前关于克罗恩病的病理生理学知识所预期的那样，来自健康对照和患病患者诱导多能干细胞的“迷你肠道”没有明显的形态差异。综上所述，我们的平台将能够以一种新型的“疾病在培养皿中”的形式对克罗恩病的病理生理学进行详细且互补的表型分析。
