Development
Author: Luciano Fiore | email: lfiore@fmed.uba.ar
Luciano Fiore 1°, Mariana Holubiec 2°, Julieta Bianchelli 2°, Alan Hallberg 1°, Gonzalo Spelzini 1°, Gabriel Scicolone 1°, Tomas Falzone 2°
1° CONICET – Universidad de Buenos Aires, Instituto de Biología Celular y Neurociencias “Prof. E. De Robertis” (IBCN), Ciudad Autónoma de Buenos Aires, Argentina. Universidad de Buenos Aires, Facultad de Medicina, Departamento de Biología Celular, Histología, Embriología y Genética, Ciudad Autónoma de Buenos Aires, Argentina.
2° Instituto de Investigación en Biomedicina (IBioBA) – CONICET – Instituto Partner de la Sociedad Max Planck, Ciudad Autónoma de Buenos Aires, Argentina. Universidad de Buenos Aires, Facultad de Medicina, Departamento de Biología Celular, Histología, Embriología y Genética, Ciudad Autónoma de Buenos Aires, Argentina
Human brain organoids allows us to recapitulate in vitro the early development of the brain. Nevertheless, one of the big limitations of this model is the lack of vascularization. In addition to the delivery of oxygen, accumulating evidence suggests that the vascular system of the brain regulates neural differentiation and circuit formation. Our aim is to develop vascularized organoids using extraembryonic chicken cells in order to obtain a faster, better and more representative model of the human brain development. The chick embryo chorioallantoic membrane (CAM) is a rich vascularized extraembryonic-membrane. Since the CAM is naturally immunodeficient, we transplanted early human neural fate organoids (neuroepithelium stage) into chicken embryos of 7 days of development (E7) WT CAM. After 5 days of incubation (E12 embryo) we opened the eggs, fixed the CAM and analyzed the engraftment organoids by immunohistochemistry and hematoxylin-eosin staining. We found that organoids got vascularized and proliferated next to the CAM vessels. We also observed cells expressing the neural marker Pax6, integrated and surrounded by allantoid derived cells that expressed TBX5. These preliminary results allow us to conclude that CAM is a suitable environment to host human brain organoids and that CAM would support the engraftment of more developed brain organoids and their growth therein could faithfully recapitulate most of the characteristics of the brain development process.