Cerebral Organoids: A Model of Brain Development
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Cerebral Organoids: A Model of Brain Development K. K. Sukhinicha, * and M. A. Aleksandrovaa a
Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, 119334 Russia *e-mail: [email protected] Received March 1, 2020; revised March 30, 2020; accepted March 31, 2020
Abstract—The development of the human brain in normal or pathological conditions is currently infeasible to fully reproduce in animal models, warranting a search for alternative solutions. Significant progress has recently been achieved in the development of methods to culture human cerebral organoids. Cerebral organoids are 3D cultures wherein brain-specific cell types develop from embryonic or induced pluripotent stem cells. As a result of the self-organization of nervous tissue, unique features of human brain development are reproduced in cerebral organoids, while being absent from the developing rodent brain. However, organoids do not exactly copy the brain, and a number of restrictions should be overcome to expand the opportunities to study the development and disorders of the human brain with their use in the future. It is clear that the modeling of cerebral organoids has already opened up prospects for both basic and clinical research. The review discusses the methods to culture nervous tissue, the means to produce cerebral organoids, the features of their self-organization, and the modeling of normal developmental processes and brain pathology with cerebral organoids. Keywords: cerebral organoids, 3D cultures, brain development, neurogenesis, human radial glia DOI: 10.1134/S1062360420040074
INTRODUCTION: BACKGROUND TO THE DESIGN OF ADEQUATE MODELS TO STUDY HUMAN BRAIN DEVELOPMENT AND THE ROLE OF 3D ORGANOIDS Studying the brain development in normal or pathological conditions is one of the central problems of neurobiology. The development of the human brain is a special problem that is difficult to solve not only because the morphological and functional organization of the brain in humans differs from that in primates and rodents but also because a limited set of allowable methods and suitable animal models are available for human brain research (Fietz and Huttner, 2011; Taverna et al., 2014; Florio et al., 2018). Rodents, mice in particular, are broadly used as laboratory mammals, and basic mechanisms of early brain development were established with their use. Genetic manipulations with the mouse genome became highly efficient and complex in recent years. However, a direct examination of human tissues is preferable over studies with rodent models in many cases because the brain development differs between mice and humans in spite of its evolutionary conservation (Lui et al., 2011). For example, an outer subventricular zone (oSVZ) forms in the developing human cerebral cortex, but it is absent in mice (Hansen et al., 2010). The oSVZ harbors outer radial glial (oRG) cells, which differ in behavior and expression of certain human-specific genes from other radial glial cells
(Taverna et al., 2014; Pollen et al., 2015;
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