Intestinal Organoids as a Novel Complementary Model to Dissect Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBDs) include colitis ulcerosa and Crohn's disease, besides the rare microscopic colitis. Both diseases show a long-lasting, relapsing-remitting, or even chronic active course with tremendous impact on quality of life. IBDs frequently cause disability, surgical interventions, and high costs; as in other autoimmune diseases, their prevalent occurrence at an early phase of life raises the burden on health care systems. Unfortunately, our understanding of the pathogenesis is still incomplete and treatment therefore largely focuses on suppressing the resulting excessive inflammation. One obstacle for deciphering the causative processes is the scarcity of models that parallel the development of the disease, since intestinal inflammation is mostly induced artificially; moreover, the intestinal epithelium, which strongly contributes to IBD pathogenesis, is difficult to assess. Recently, the development of intestinal epithelial organoids has overcome many of those problems. Here, we give an overview on the current understanding of the pathogenesis of IBDs with reference to the limitations of previous well-established experimental models. We highlight the advantages and detriments of recent organoid-based experimental setups within the IBD field and suggest possible future applications.

"Miniguts" from plucked human hair meet Crohn's disease.

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.

Brain necrosis after radiotherapy for primary intracerebral tumor.

Radiotherapy is a standard postoperative treatment for cerebral glioma. We have observed the onset of symptoms related to brain necrosis, as opposed to recurrent tumor, in surviving patients. This has been manifest as dementia with a computed tomographic pattern of low density in the frontal lobe uninvolved with tumor, but within the field of radiotherapy. Two patients presented with mass lesions also unrelated to recurrent tumor. We question the necessity of full brain irradiation and suggest that radiotherapy techniques be altered to target the tumor and not encompass the entire brain.