Scientists have set up a new system of vascularized brain organ culture.

Wang Xiaoqun's research group, Institute of Biophysics, Chinese Academy of Sciences, has long been committed to the study of brain development and function. In recent years, the research group has systematically analyzed cell types and cell characteristics during the embryonic development of human cerebral cortex, and revealed the regulatory mechanism of rapid growth of human brain neurons and generation of sulcus and gyrus during embryonic development (Liu et al., 2017; Zhong et al., 2018).cross species studies have shown that the development of cerebral cortex in human and non-human primates presents some characteristics different from other lower animals (such as rodents), such as the appearance of the lateral subventricular area (osvz region), which contains a large number of Org neural precursor cells and IPC intermediate neural precursor cells (IPC) (Wang et al, The diversity and abundance of these neural precursor cells promote the high-speed production of neurons and provide a cellular basis for the complex functional development of the human brain.in order to further study this field, Wang Xiaoqun's research group first established the technology of cortical like culture as early as 2012, and applied this technology to simulate the development and development process of microcephaly caused by ASPM gene mutation in vitro, and studied its pathological characteristics (Li et al., 2017).at present, compared with the traditional two-dimensional culture method, three-dimensional brain like organs have the development characteristics and structure similar to the human brain, and can well simulate the dynamic changes of cell types and the formation of neural circuits.therefore, three-dimensional brain like organs are more and more used in the study of early development of human brain in recent years.in addition, brain like organs also show broad application prospects in exploring the pathological mechanism of brain diseases and high-throughput drug screening.however, due to the lack of participation of the circulatory system, the traditional long-term culture of brain like organs is largely limited by the hypoxia and cell death caused by the insufficient supply of oxygen and nutrients, which makes the long-term culture of brain like organs impossible.on May 13, Wang Xiaoqun and Professor Wu Qian of Beijing Normal University published a paper entitled vasculated human cortical organoids (vorganoid) model cortical development in vivo online in PLoS Biology.in this study, a method of obtaining vascularized brain like organs was established by co culture of human embryonic stem cells (or human pluripotent stem cells) and human umbilical vein endothelial cells (HUVECs), which solved the problem of oxygen and nutrient deficiency which restricted the long-term development of brain like organs.this study also confirmed that the vascular network of HUVECs can accelerate the maturation and development of brain like organs and make them mature earlier. After transplantation in vivo, endothelial cells in the vascular network of brain like organs can be integrated into the blood vessels of host mice to form a new functional vascular network with blood flow. In addition, patch clamp whole cell recording showed that neurons in vascularized brain like organs were able to emit action potentials and establish extensive synaptic connections of electrical burst touch chemistry.these results indicate that the vascularized brain like organ established in this study can simulate the characteristics of human embryonic cerebral cortex in cell type, cell arrangement, transcriptome pattern and electrophysiological characteristics, so it is a good model for the study of human cortical development and related diseases.in addition, in order to explore the possibility of brain like organs in transplantation, the researchers transplanted vascularized brain like organs into S1 brain region of immune deficient mice.studies have found that the vascular network of brain like organs can be integrated into the blood vessels of host mice to form a new functional network with blood flow, and reduce the apoptosis of grafts.brain like organs are expected to be used in the further research or treatment of brain diseases in the future, such as the treatment and application of brain trauma.the establishment of vascularized brain like organs will provide a new research idea and scheme for optimizing the culture of brain like organs, promoting their functional maturity, and establishing three-dimensional blood-brain barrier model in vitro, which has important biological and medical application potential.the research was completed by the Institute of Biophysics, Chinese Academy of Sciences and Beijing Normal University.Institute of Biophysics, Shi Yingchao, sun Le, Wang Mengdi and Liu Jianwei are co first authors of the paper.the research was supported by the leading projects of the Chinese Academy of Sciences, the national key R & D plan and the NSFC projects.in addition, the flow separation platform and experimental animal feeding platform of the Institute of Biophysics provided support for the research.Fig