Abstract<\/strong><\/p>\n Recent studies have demonstrated an array of stem cell\u2013derived, self-organizing miniature organs, termed organoids, that replicate the key structural and functional characteristics of their in vivo counterparts. As organoid technology opens up new frontiers of research in biomedicine, there is an emerging need for innovative engineering approaches for the production, control, and analysis of organoids and their microenvironment. In this Review, we explore organ-on-a-chip technology as a platform to fulfill this need and examine how this technology may be leveraged to address major technical challenges in organoid research. We also discuss emerging opportunities and future obstacles for the development and application of organoid-on-a-chip technology.<\/p>\n<\/div>\n Decades of study in developmental biology and stem cell research have advanced our ability to recapitulate the key aspects of organogenesis in vitro. Recent years have seen considerable progress toward exploiting the self-organizing properties of pluripotent or adult stem cells to generate organotypic multicellular constructs known as organoids (1<\/em><\/a>,\u00a02<\/em><\/a>). Thanks to their ability to emulate microarchitecture and functional characteristics of native organs, organoids are emerging as a promising approach for the modeling of development, homeostasis, and disease of various human organs (1<\/em><\/a>\u20133<\/em><\/a>).<\/p>\n <\/p>\n The conventional methods of forming organoids rely on three-dimensional (3D) culture of mammalian stem cells with sequential addition of growth factors. Although this approach has been widely used because of its simplicity, there is growing recognition that the current organoid culture techniques have the potential for substantial improvement. In particular, the random configuration of traditional 3D culture makes it difficult to precisely control organoids and their local environment. Existing culture systems also have limited capacity to reproduce the complex and dynamic microenvironment of a developing organ that provides instructive cues for organogenesis (4<\/em><\/a>,\u00a05<\/em><\/a>). The lack of these environmental signals poses challenges to achieving more complete, in vivo\u2013like organoid development in a reproducible manner (3<\/em><\/a>,\u00a06<\/em><\/a>).<\/p>\n To address the limitations of conventional culture techniques, researchers in stem cell and developmental biology are forming alliances with engineers and physical scientists to develop advanced in vitro technologies for organoid research. At the forefront of this undertaking is the integration of organoids with organ-on-a-chip technology.<\/p>\n <\/p>\n What are organs-on-a-chip?<\/strong><\/p>\n Organs-on-a-chip can be broadly defined as microfabricated cell culture devices designed to model the functional units of human organs in vitro (7<\/em><\/a>\u201312<\/em><\/a>). In general, the construction of any organ-on-a-chip system is guided by design principles based on a reductionist analysis of its target organ (Fig. 1<\/a>). The first step is to understand the anatomy of the target organ and reduce it to the basic elements essential for physiological function. These functional units are then examined to identify key features such as different cell types, structural organization, and organ-specific biochemical and physical microenvironments. For example, the alveolar\u2013capillary unit of the lung consists of alveolar epithelial cells (cell type 1) and pulmonary microvascular endothelial cells (cell type 2) that are closely apposed to each other and separated by a thin interstitium (structural organization) (Fig. 1A<\/a>). The epithelial and endothelial layers are subjected to air and blood flow, respectively, and the multilayered interface experiences breathing-induced cyclic mechanical stretch (organ-specific microenvironment).<\/p>\n <\/p>\n (A<\/strong>) Reductionist analysis of a target organ (lung) identifies alveoli as the functional unit composed of epithelial and endothelial cells separated by a thin interstitium. (B<\/strong>) An analogous model is constructed from three layers to bring these two cell types into physiological proximity. (C<\/strong>) To mimic breathing-induced mechanical activity, the cells are cyclically stretched by applying vacuum (vac) to the side chambers. [Illustration: BIOLines Lab]<\/p>\n <\/p>\n <\/p>\n<\/div>\n<\/figcaption><\/figure>\n Next, a cell culture device is designed to replicate the identified features. The device often contains multiple, individually addressable flow-through microchambers to grow multiple cell types while controlling the culture environment in a cell type\u2013dependent manner. If necessary, additional components are incorporated that can be actuated mechanically, chemically, electromagnetically, or optically to emulate the biochemical and mechanical environment of the target organ. Finally, the designed device is produced using microfabrication techniques such as soft lithography (13<\/em><\/a>).<\/p>\n The design strategy outlined here has been successfully implemented to create an organ-on-a-chip model of the alveolar\u2013capillary unit of the lung (14<\/em><\/a>). This system consists of two overlapping microchannels separated by a thin, flexible, microporous membrane (Fig. 1B<\/a>, left). The compartmentalized design enables coculture of alveolar epithelial cells and lung microvascular endothelial cells on either side of the membrane while the cells are exposed to their respective tissue-specific environment (i.e., air on the alveolar side and fluid flow on the vascular side) (Fig. 1B<\/a>, right). To mimic the deformation of the alveolar\u2013capillary interface during breathing, the device is also equipped with two hollow microchambers alongside the culture channels, in which cyclic vacuum application induces stretching of the cell-lined intervening membrane (Fig. 1C<\/a>).<\/p>\n By integrating living human cells with synthetically generated yet physiologically relevant microenvironments, organs-on-a-chip can mimic integrated organ-level functions necessary for physiological homeostasis, as well as complex disease processes (15<\/em><\/a>,\u00a016<\/em><\/a>). Furthermore, different organ-chip models can be fluidically linked to construct \u201cbody-on-a-chip\u201d systems capable of simulating multiorgan interactions and physiological responses at the systemic level (17<\/em><\/a>,\u00a018<\/em><\/a>). Although these advanced model systems are still far from achieving the functionality of real human organs, their ability to capture key aspects of human physiology and pathophysiology makes them a promising approach for complementing and reducing animal studies for preclinical assessment of drugs, medical devices, and biomaterials (7<\/em><\/a>,\u00a09<\/em><\/a>,\u00a019<\/em><\/a>). Organ-on-a-chip technology also provides an attractive in vitro platform for screening adverse health effects of chemicals, environmental materials, and consumer products (10<\/em><\/a>,\u00a020<\/em><\/a>).<\/p>\n<\/div>\n <\/p>\n <\/p>\n <\/p>\n (\uc6d0\ubb38: \uc5ec\uae30<\/a>\ub97c \ud074\ub9ad\ud558\uc138\uc694~)<\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n Abstract<\/strong><\/p>\n Organoids are microscopic self-organizing, three-dimensional structures that are grown from stem cells in vitro. They recapitulate many structural and functional aspects of their in vivo counterpart organs. This versatile technology has led to the development of many novel human cancer models. It is now possible to create indefinitely expanding organoids starting from tumor tissue of individuals suffering from a range of carcinomas. Alternatively, CRISPR-based gene modification allows the engineering of organoid models of cancer through the introduction of any combination of cancer gene alterations to normal organoids. When combined with immune cells and fibroblasts, tumor organoids become models for the cancer microenvironment enabling immune-oncology applications. Emerging evidence indicates that organoids can be used to accurately predict drug responses in a personalized treatment setting. Here, we review the current state and future prospects of the rapidly evolving tumor organoid field.<\/p>\n <\/p>\n <\/p>\n (\uc6d0\ubb38: \uc5ec\uae30<\/a>\ub97c \ud074\ub9ad\ud558\uc138\uc694~)<\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n \uc2e4\uc81c \uc870\uc9c1\uc774\ub098 \uc7a5\uae30\uc640 \ub2ee\uc740 \uc624\uac00\ub178\uc774\ub4dc\ub97c \uc774\uc6a9\ud558\uba74 \ubcd1\uc758 \uc6d0\uc778\uc774\ub098 \uc9c4\ud589 \uacfc\uc815\uc744 \ubc1d\ud788\uac70\ub098 \uc2e0\uc57d\uc758 \ud6a8\uacfc \ub4f1\uc744 \ud655\uc778\ud560 \uc218 \uc788\ub2e4. \uc0ac\uc774\uc5b8\uc2a4 \uc81c\uacf5<\/em><\/span><\/p>\n <\/p>\n <\/p>\n \uad6d\uc81c\ud559\uc220\uc9c0 \uc0ac\uc774\uc5b8\uc2a4\ub294 7\uc77c \uc778\uac04\uc758 \uae30\ub3c4\ub97c \ud749\ub0b4 \ub0b8 \uc624\uac00\ub178\uc774\ub4dc\ub97c 3\ucc28\uc6d0 \uacf5\ucd08\uc810\ud604\ubbf8\uacbd\uc73c\ub85c \ucd2c\uc601\ud55c \uc0ac\uc9c4\uc744 \ud45c\uc9c0\ub85c \ub2f4\uc558\ub2e4. \ud30c\ub780\uc0c9\uc774\u00a0DNA,<\/span>\u00a0\ube68\uac04\uc0c9\uc774 \ub2e8\ubc31\uc9c8\uc774\ub2e4. \uc0ac\uc774\uc5b8\uc2a4\ub294 \uc774\ubc88 \ud2b9\uc9d1\uae30\uc0ac\uc5d0\uc11c \uc2ed\uc218\ub144\uac04 \uacfc\ud559\uc790\ub4e4\uc774 \uc624\uac00\ub178\uc774\ub4dc\ub97c \ub9cc\ub4e4\uc5b4 \uc5f0\uad6c\ud55c \uacb0\uacfc\ub97c \ucd1d\uc815\ub9ac\ud588\ub2e4.<\/p>\n \uc624\uac00\ub178\uc774\ub4dc\ub294 \uc904\uae30\uc138\ud3ec\ub97c 3\ucc28\uc6d0\uc73c\ub85c \uc313\uc544 \ubc30\uc591\ud55c \uac83\uc73c\ub85c \uc2e4\uc81c \uc870\uc9c1\uacfc \ub2ee\uc544 \uc57d\ubb3c \ud6a8\uacfc\ub098 \uc9c8\ubcd1 \uc6d0\uc778, \uc0dd\ub9ac\uc801\uc778 \ubc18\uc751 \ub4f1\uc744 \uc5f0\uad6c\ud560 \ub54c \uc0ac\uc6a9\ud55c\ub2e4. \ub3d9\ubb3c\uc5d0\uac8c \uc2e4\ud5d8\ud560 \ub54c\ubcf4\ub2e4 \ud6e8\uc52c \uc815\ud655\ud55c \uacb0\uacfc\ub97c \uc5bb\uc744 \uc218 \uc788\uace0, \uc0b4\uc544 \uc788\ub294 \uc0ac\ub78c\uc5d0\uac8c \ud560 \uc218 \uc5c6\ub294 \uc2e4\ud5d8\uae4c\uc9c0 \ud560 \uc218 \uc788\ub2e4\ub294 \uc7a5\uc810\uc774 \uc788\ub2e4. \uc624\uac00\ub178\uc774\ub4dc\uac00 \uc778\uccb4\ub97c \ub300\uccb4\ud558\uae30 \uc704\ud574\uc11c\ub294 \uc2e4\uc81c \uc138\ud3ec \ub0b4\uc5d0\uc11c \uc77c\uc5b4\ub098\ub294 \ud604\uc0c1\uacfc \ubbf8\uc138\ud658\uacbd\uc774 \ub2ee\uc544\uc57c \ud558\uace0, \uc678\ubd80\uc5d0\uc11c \uc778\uc704\uc801\uc73c\ub85c \uc870\uc808\ud560 \uc218 \uc788\uc5b4\uc57c \ud55c\ub2e4.<\/p>\n \uba3c\uc800 \ud55c\uc2a4 \ud074\ub808\ubc84\uc2a4 \ub124\ub35c\ub780\ub4dc \uc704\ud2b8\ub808\ud750\ud2b8 \uc758\ud559\uc5f0\uad6c\uc18c \uad50\uc218\uc640 \ub370\uc774\ube44\ub4dc \ud22c\ubca0\uc2a8 \ubbf8\uad6d \ub85c\uc2a4\uac00\ub974\ud150 \uc5f0\uad6c\uc7ac\ub2e8 \ucdcc\uc7a5\uc554 \uc5f0\uad6c\uc18c \uc218\uc11d \uc5f0\uad6c\uc6d0 \uacf5\ub3d9\uc5f0\uad6c\ud300\uc740 \uadf8\uac04 \uacfc\ud559\uc790\ub4e4\uc774 \uc554\uc744 \uc5f0\uad6c\ud558\uae30 \uc704\ud574 \uc624\uac00\ub178\uc774\ub4dc\ub97c \ub9cc\ub4e4\uc5c8\ub358 \uc5f0\uad6c \uacb0\uacfc\ub97c \uc18c\uac1c\ud588\ub2e4. \uc554\uc774 \ubc1c\uc0dd\ud558\ub294 \uc6d0\uc778\uc744 \ucc3e\uac70\ub098, \uc554\uc774 \uc804\uc774\ub418\ub294 \uacfc\uc815, \ub610\ub294 \uc0c8\ub85c \uac1c\ubc1c\ud55c \ud56d\uc554\uc81c\uc758 \ud6a8\uacfc\ub97c \ud655\uc778\ud560 \ub54c \uc624\uac00\ub178\uc774\ub4dc\ub97c \uc4f8 \uc218 \uc788\ub2e4.<\/p>\n \ud074\ub808\ubc84\uc2a4 \uad50\uc218\ub294 “\uccb4\ub0b4\uc5d0\uc11c \uc554\uc774 \ubc1c\uacac\ub418\uba74 \ube68\ub9ac \uc5c6\uc560\uc57c \ud558\ub294\ub370, \uc554\uc5d0 \ub300\ud574 \uc5f0\uad6c\ud558\ub824\uba74 \uc624\ub7ab\ub3d9\uc548 \uc0b4\uc544 \uc788\ub294 \uc554 \uc870\uc9c1 \uc0d8\ud50c\uc774 \ub9ce\uc774 \ud544\uc694\ud558\ub2e4”\uba74\uc11c “\uc554\uc870\uc9c1\uc744 \ud749\ub0b4 \ub0b8 \uc624\uac00\ub178\uc774\ub4dc\uac00 \ud655\uc2e4\ud55c \ub3c4\uad6c”\ub77c\uace0 \ub9d0\ud588\ub2e4. \uadf8\ub294 “\uc608\ub97c \ub4e4\uc5b4\u00a0MLH<\/span>1,\u00a0APC<\/span>\ucc98\ub7fc \ub3cc\uc5f0\ubcc0\uc774\uac00 \uc0dd\uacbc\uc744 \ub54c \uc554\uc744 \uc720\ubc1c\ud558\ub294 \uac83\uc73c\ub85c \uc54c\ub824\uc9c4 \uc720\uc804\uc790\ub97c \uc5f0\uad6c\ud558\uae30 \uc704\ud574 \ud06c\ub9ac\uc2a4\ud37c \uc720\uc804\uc790 \uac00\uc704\ub85c \uc774 \uc720\uc804\uc790\ub4e4\uc744 \uc5c6\uc564 \uc138\ud3ec\ub4e4\uc744 \uc624\uac00\ub178\uc774\ub4dc\ub85c \ubc30\uc591\ud55c\ub2e4”\uba70 “\uc554\uc774 \uc5b4\ub5bb\uac8c \ubc1c\uc0dd\ud558\ub294\uc9c0 \uacfc\uc815\uc744 \uad00\ucc30\ud558\uac70\ub098, \uc554\uc870\uc9c1 \uc8fc\ubcc0\uc758 \ubbf8\uc138\ud658\uacbd\uc744 \uc5f0\uad6c\ud560 \uc218 \uc788\ub2e4”\uace0 \uc18c\uac1c\ud588\ub2e4.<\/p>\n \uacfc\ud559\uc790\ub4e4\uc774 \uc554 \uc624\uac00\ub178\uc774\ub4dc\ub97c \ud65c\uc6a9\ud558\uba74 \uac1c\uc778 \ub9de\ucda4\ud615 \uce58\ub8cc\ub3c4 \uc124\uacc4\ud560 \uc218 \uc788\uc744 \uc804\ub9dd\uc774\ub2e4. \ud658\uc790\ub9c8\ub2e4 \uc5b4\ub5a4 \uc720\uc804\uc790\uc5d0 \ub3cc\uc5f0\ubcc0\uc774\uac00 \uc788\uc5b4 \uc554\uc774 \ubc1c\uc0dd\ud588\ub294\uc9c0 \uc6d0\uc778\uc744 \ucc3e\uac70\ub098, \uac1c\ubcc4 \ud56d\uc554\uc81c\uc758 \uce58\ub8cc\ud6a8\uacfc\uac00 \uc5b4\ub5bb\uac8c \ub098\ud0c0\ub098\ub294\uc9c0 \ubbf8\ub9ac \uc54c \uc218 \uc788\uae30 \ub54c\ubb38\uc774\ub2e4.<\/p>\n \ud074\ub808\ubc84\uc2a4 \uad50\uc218\ub294 “\ucd5c\uadfc\uc5d0\ub294 \ud56d\uc554\uce58\ub8cc \uc911\uc5d0 \uc554\uc138\ud3ec\uc640 \uba74\uc5ed\uc138\ud3ec\uac00 \uc11c\ub85c \uc5b4\ub5a4 \uc791\uc6a9\uc744 \ud558\ub294\uc9c0, \uc5b4\ub5bb\uac8c \ud558\uba74 \uba74\uc5ed\uc138\ud3ec\uac00 \uc554\uc138\ud3ec\ub97c \uacf5\uaca9\ud558\uac8c \ub9cc\ub4e4 \uc218 \uc788\ub294\uc9c0 \ub4f1\ub3c4 \uc624\uac00\ub178\uc774\ub4dc\ub85c \uc5f0\uad6c\ud558\uace0 \uc788\ub2e4”\uace0 \ub9d0\ud588\ub2e4. \uacfc\ud559\uc790\ub4e4\uc740 \uc904\uae30\uc138\ud3ec\ub97c \uc5b4\ub5bb\uac8c \uc313\uc544\uc57c \uc2e4\uc81c \uc870\uc9c1\uacfc \ube44\uc2b7\ud55c \uc624\uac00\ub178\uc774\ub4dc\ub97c \ub514\uc790\uc778\ud560 \uc218 \uc788\ub294\uc9c0\uc5d0 \ub300\ud574\uc11c\ub3c4 \uc5f0\uad6c\ud558\uace0 \uc788\ub2e4.<\/p>\n \ud0c0\uce74\ub178\ub9ac \ud0c0\ucf00\ubca0 \uc77c\ubcf8 \ub3c4\ucfc4\uc758\uacfc\uce58\uacfc\ub300 \uad50\uc218\uc640 \uc81c\uc784\uc2a4 \uc6f0\uc2a4 \ubbf8\uad6d \uc2e0\uc2dc\ub0b4\ud2f0\uc5b4\ub9b0\uc774\ubcd1\uc6d0 \ub0b4\ubd84\ube44\ub0b4\uacfc \uad50\uc218 \uacf5\ub3d9\uc5f0\uad6c\ud300\uc774\ub098 \ub9c9\ub2ec\ub808\ub098 \uc81c\ub974\ub2c8\uce74-\uac9f\uce20 \uc601\uad6d \ucf00\uc784\ube0c\ub9ac\uc9c0\ub300 \uc0dd\ub9ac\ud559\uacfc \ud3ec\uc720\ub3d9\ubb3c\ubc30\uc544\ubc0f\uc904\uae30\uc138\ud3ec\uc5f0\uad6c\uc18c \uad50\uc218\ud300 \ub4f1\uc740 \uc624\uac00\ub178\uc774\ub4dc\uac00 \uc2e4\uc81c \uc7a5\uae30\ucc98\ub7fc \uc131\uc7a5\ud558\uace0 \uc0dd\ub9ac\uc801\uc73c\ub85c \uae30\ub2a5\ud558\ub824\uba74 3\ucc28\uc6d0 \ud615\ud0dc\uc640 \uad6c\uc870\uac00 \uc2e4\uc81c\uc640 \ube44\uc2b7\ud574\uc57c \ud55c\ub2e4\uace0 \uc0dd\uac01\ud55c\ub2e4. \uadf8\ub798\uc11c \ubc30\uc544 \ubc1c\uc0dd \uc911\uc5d0 \uc904\uae30\uc138\ud3ec\uac00 \uac01 \uc138\ud3ec\ub85c \ubd84\ud654\ud558\uba74\uc11c \uc5b4\ub5bb\uac8c \ubc30\uc5f4\ub418\uace0 \uac01 \uae30\uad00\uc744 \ud615\uc131\ud558\ub294\uc9c0 \uad00\ucc30\ud574 \uadf8 \ub2f5\uc744 \ucc3e\uace0 \uc788\ub2e4.<\/p>\n \uc81c\ub974\ub2c8\uce74-\uac9f\uce20 \uad50\uc218\ud300\uc740 \uc9c0\ub09c\ud574 3\uc6d4 \uc950\uc758 \ubc30\uc544\uc904\uae30\uc138\ud3ec\ub97c \uc313\uc544 \uc778\uacf5 \ubc30\uc544\ub97c \ub9cc\ub4dc\ub294 \uc2e4\ud5d8\uc5d0 \uc131\uacf5\ud55c \uc5f0\uad6c \uacb0\uacfc\ub97c \uc0ac\uc774\uc5b8\uc2a4\uc5d0 \uc2e3\uae30\ub3c4 \ud588\ub2e4. \ub2f9\uc2dc \uc5f0\uad6c\ud300\uc774 \ub9cc\ub4e0 \uc778\uacf5 \ubc30\uc544\ub294 \uc2e4\uc81c \uc950\uc758 \ubc30\uc544\uc640 \ud615\ud0dc\uc640 \uc0dd\ub9ac\ud65c\uc131\uc774 \ub9e4\uc6b0 \ube44\uc2b7\ud558\ub2e4\ub294 \ud3c9\uac00\ub97c \ubc1b\uc558\ub2e4.<\/p>\n <\/p>\n <\/p>\n <\/p>\n (\uc6d0\ubb38: \uc5ec\uae30<\/a>\ub97c \ud074\ub9ad\ud558\uc138\uc694~)<\/p>\n <\/p>\n <\/p>\n <\/p>\n","protected":false},"excerpt":{"rendered":"![](\"https:\/\/science.sciencemag.org\/content\/sci\/364\/6444\/960\/F1.medium.gif\")
<\/span><\/a><\/div>\n\n
<\/h5>\n
Cancer modeling meets human organoid technology<\/h5>\n
\ud56d\uc554\u00b7\ub9de\ucda4\uce58\ub8cc \ud601\uba85 \uac00\uc838\uc62c ‘\uc624\uac00\ub178\uc774\ub4dc’<\/h5>\n
![\"\"](\"https:\/\/imgnews.pstatic.net\/image\/584\/2019\/06\/09\/0000004698_001_20190609060023938.jpg?type=w647\")
<\/span><\/p>\n