Organoid

An organoid is a miniaturized and simplified version of an organ produced in vitro in three dimensions that shows realistic micro-anatomy. They are derived from one or a few cells from a tissue, embryonic stem cells or induced pluripotent stem cells, which can self-organize in three-dimensional culture owing to their self-renewal and differentiation capacities. The technique for growing organoids has rapidly improved since the early 2010s, and it was named by The Scientist as one of the biggest scientific advancements of 2013. Organoids are used by scientists to study disease and treatments in a laboratory. An organoid is a miniaturized and simplified version of an organ produced in vitro in three dimensions that shows realistic micro-anatomy. They are derived from one or a few cells from a tissue, embryonic stem cells or induced pluripotent stem cells, which can self-organize in three-dimensional culture owing to their self-renewal and differentiation capacities. The technique for growing organoids has rapidly improved since the early 2010s, and it was named by The Scientist as one of the biggest scientific advancements of 2013. Organoids are used by scientists to study disease and treatments in a laboratory. Attempts to create organs in vitro started with one of the first dissociation-reaggregation experiments where Henry Van Peters Wilson demonstrated that mechanically dissociated sponge cells can reaggregate and self-organize to generate a whole organism. In the subsequent decades, multiple labs were able to generate different types of organs in vitro through the dissociation and reaggregation of organ tissues obtained from amphibians and embryonic chicks. The phenomena of mechanically dissociated cells aggregating and reorganizing to reform the tissue they were obtained from subsequently led to the development of the differential adhesion hypothesis by Malcolm Steinberg.With the advent of the field of stem cell biology, the potential of stem cells to form organs in vitro was realized early on with the observation that when stem cells form teratomas or embryoid bodies, the differentiated cells can organize into different structures resembling those found in multiple tissue types. The advent of the field of organoids, started with a shift from culturing and differentiating stem cells in 2D media, to 3D media to allow for the development of the complex 3-dimensional structures of organs. Since 1987, researchers have devised different methods for 3-D culturing, and were able to utilize different types of stem cells to generate organoids resembling a multitude of organs.In 2008, Yoshiki Sasai and his team at RIKEN institute demonstrated that stem cells can be coaxed into balls of neural cells that self-organize into distinctive layers. In 2009 the Laboratory of Hans Clevers at Hubrecht Institute and University Medical Center Utrecht, The Netherlands showed that single LGR5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. In 2010, Mathieu Unbekandt & Jamie A. Davies demonstrated the production of renal organoids from murine fetus-derived renogenic stem cells: subsequent reports showed significant physiological function of these organoids in vitro and in vivo. In 2013, Madeline Lancaster at the Austrian Academy of Sciences established a protocol for culturing cerebral organoids derived from stem cells that mimic the developing human brain's cellular organization.In 2014, Artem Shkumatov et al. at the University of Illinois at Urbana-Champaign demonstrated that cardiovascular organoids can be formed from ES cells through modulation of the substrate stiffness, to which they adhere. Physiological stiffness promoted three-dimensionality of EBs and cardiomyogenic differentiation. Takebe et al. demonstrate a generalized method for organ bud formation from diverse tissues by combining pluripotent stem cell-derived tissue-specific progenitors or relevant tissue samples with endothelial cells and mesenchymal stem cells. They suggested that the less mature tissues, or organ buds, generated through the self-organized condensation principle might be the most efficient approach toward the reconstitution of mature organ functions after transplantation, rather than condensates generated from cells of a more advanced stage. Lancaster and Knoblich define an organoid as a collection of organ-specific cell types that develops from stem cells or organ progenitors, self-organizes through cell sorting and spatially restricted lineage commitment in a manner similar to in vivo, and exhibits the following properties: Organoid formation generally requires culturing the stem cells or progenitor cells in a 3D medium. The 3D medium can be made using an extracellular matrix hydrogel Matrigel, which is a laminin-rich extracellular matrix that is secreted by the Engelbreth-Holm-Swarm tumor line. Organoid bodies can then be made through embedding stem cells in the 3D medium. When pluripotent stem cells are used for the creation of the organoid, the cells are usually, but not all the time, allowed to form embryoid bodies. Those embryoid bodies are then pharmacologically treated with patterning factors to drive the formation of the desired organoid identity. Organoids have also been created using adult stem cells extracted from the target organ, and cultured in 3D media. Cancer organoids have also been created in an effort to create in vitro models other than conventional cell lines. A multitude of organ structures have been recapitulated using organoids. This section aims to outline the state of the field as of now through providing an abridged list of the organoids that have been successfully created, along with a brief outline based on the most recent literature for each organoid, and examples of how it has been utilized in research. A cerebral organoid describes artificially grown, in vitro, miniature organs resembling the brain. Cerebral organoids are created by culturing human pluripotent stem cells in a three-dimensionalrotational bioreactor and develop over a course of months. Gut organoids refer to organoids that recapitulate structures of the gastrointestinal tract. The gastrointestinal tract arises from the endoderm, which during development forms a tube that can be divided in three distinct regions, which give rise to, along with other organs, the following sections of the gastrointestinal tract: