Despite remaining the best in vitro model to resemble the human brain, a weakness of human cerebral organoids is the lack of the endothelial component that in vivo organizes in the blood brain barrier (BBB). Since the BBB is crucial to control the microenvironment of the nervous system, this study proposes a co-culture of BBB and cerebral organoids. We utilized a BBB model consisting of primary human brain microvascular endothelial cells and astrocytes in a transwell system. Starting from induced Pluripotent Stem Cells (iPSCs) we generated human cerebral organoids which were then cultured in the absence or presence of an in vitro model of BBB to evaluate potential effects on the maturation of cerebral organoids. By morphological analysis, it emerges that in the presence of the BBB the cerebral organoids are better organized than controls in the absence of the BBB. This effect might be due to Brain Derived Neurotrophic Factor (BDNF), a neurotrophic factor released by the endothelial component of the BBB, which is involved in neurodevelopment, neuroplasticity and neurosurvival.

The presence of BBB hastens neuronal differentiation of cerebral organoids - The potential role of endothelial derived BDNF / G. Fedele, A. Cazzaniga, S. Castiglioni, L. Locatelli, A. Tosoni, M. Nebuloni, J.A.M. Maier. - In: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. - ISSN 0006-291X. - 626:(2022 Oct 20), pp. 30-37. [10.1016/j.bbrc.2022.07.112]

The presence of BBB hastens neuronal differentiation of cerebral organoids - The potential role of endothelial derived BDNF

G. Fedele
Primo
;
A. Cazzaniga
Secondo
;
S. Castiglioni;L. Locatelli;M. Nebuloni
Penultimo
;
2022

Abstract

Despite remaining the best in vitro model to resemble the human brain, a weakness of human cerebral organoids is the lack of the endothelial component that in vivo organizes in the blood brain barrier (BBB). Since the BBB is crucial to control the microenvironment of the nervous system, this study proposes a co-culture of BBB and cerebral organoids. We utilized a BBB model consisting of primary human brain microvascular endothelial cells and astrocytes in a transwell system. Starting from induced Pluripotent Stem Cells (iPSCs) we generated human cerebral organoids which were then cultured in the absence or presence of an in vitro model of BBB to evaluate potential effects on the maturation of cerebral organoids. By morphological analysis, it emerges that in the presence of the BBB the cerebral organoids are better organized than controls in the absence of the BBB. This effect might be due to Brain Derived Neurotrophic Factor (BDNF), a neurotrophic factor released by the endothelial component of the BBB, which is involved in neurodevelopment, neuroplasticity and neurosurvival.
BDNF; Blood-brain barrier; Cerebral organoids; Induced pluripotent stem cells; Brain-Derived Neurotrophic Factor; Cell Differentiation; Endothelial Cells; Humans; Blood-Brain Barrier; Induced Pluripotent Stem Cells; Organoids
Settore MED/04 - Patologia Generale
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/939480
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