Guided self-organization and cortical plate formation in human brain organoids.

Three-dimensional cell culture models have either relied on the self-organizing properties of mammalian cells or used bioengineered constructs to arrange cells in an organ-like configuration. While self-organizing organoids excel at recapitulating early developmental events, bioengineered constructs reproducibly generate desired tissue architectures. Here, we combine these two approaches to reproducibly generate human forebrain tissue while maintaining its self-organizing capacity. We use poly(lactide-co-glycolide) copolymer (PLGA) fiber microfilaments as a floating scaffold to generate elongated embryoid bodies. Microfilament-engineered cerebral organoids (enCORs) display enhanced neuroectoderm formation and improved cortical development. Furthermore, reconstitution of the basement membrane leads to characteristic cortical tissue architecture, including formation of a polarized cortical plate and radial units. Thus, enCORs model the distinctive radial organization of the cerebral cortex and allow for the study of neuronal migration. Our data demonstrate that combining 3D cell culture with bioengineering can increase reproducibility and improve tissue architecture

Transcriptome-wide Analysis Reveals Hallmarks of Human Intestine Development and Maturation InVitro and InVivo

© 2015 The Authors. Human intestinal organoids (HIOs) are a tissue culture model in which small intestine-like tissue is generated from pluripotent stem cells. By carrying out unsupervised hierarchical clustering of RNA-sequencing data, we demonstrate tha

Generation and Culture of Tumor and Metastatic Organoids from Murine Models of Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy that is refractory to all current therapies. Research into the mechanisms driving this cancer is the key to developing better diagnostic and treatment options which are urgently needed in the clinic. Genetically engineered mouse models of PDA have been valuable research tools, enabling studies of all stages of PDA progression. However, these models are difficult and time-consuming to breed, and engineering further mutations into these models requires additional time. Recently, organoid cultures of PDA have emerged as alternative models for this disease. Organoids can be rapidly generated from mouse models of PDA and enable genetic and biochemical perturbation of all stages of PDA progression. Here, we describe the generation and propagation of organoid models from PDA tumors and metastases harvested from genetically engineered mouse models