hiPSC-derived neural stem cells from patients with schizophrenia induce an impaired angiogenesis

Translational Psychiatry
Bárbara S CasasVerónica Palma

Abstract

Schizophrenia is a neurodevelopmental disease characterized by cerebral connectivity impairment and loss of gray matter. It was described in adult schizophrenia patients (SZP) that concentration of VEGFA, a master angiogenic factor, is decreased. Recent evidence suggests cerebral hypoperfusion related to a dysfunctional Blood Brain Barrier (BBB) in SZP. Since neurogenesis and blood-vessel formation occur in a coincident and coordinated fashion, a defect in neurovascular development could result in increased vascular permeability and, therefore, in poor functionality of the SZP's neurons. Here, we characterized the conditioned media (CM) of human induced Pluripotent Stem Cells (hiPSC)-derived Neural Stem Cells of SZP (SZP NSC) versus healthy subjects (Ctrl NSC), and its impact on angiogenesis. Our results reveal that SZP NSC have an imbalance in the secretion and expression of several angiogenic factors, among them non-canonical neuro-angiogenic guidance factors. SZP NSC migrated less and their CM was less effective in inducing migration and angiogenesis both in vitro and in vivo. Since SZP originates during embryonic brain development, our findings suggest a defective crosstalk between NSC and endothelial cells (EC) during the ...Continue Reading

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Citations

Feb 6, 2019·Fluids and Barriers of the CNS·Richard F KeepLester R Drewes
Jul 11, 2019·Oncology Letters·Wei CaoXianghong Yang
May 24, 2020·Communications Biology·Mayna S GomideElibio Rech
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Jun 4, 2021·BMC Bioinformatics·Gulden OlgunOznur Tastan
Jun 30, 2021·Stem Cell Research·Carolina da S G PedrosaMarília Zaluar P Guimarães
Nov 26, 2021·Bioscience Reports·Gabriela Assis-de-LemosAntonio Galina

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Methods Mentioned

BETA
biopsies
Profiler
proteome array

Software Mentioned

Image J
Graphpad Prism
ImageJ
Operetta
Harmony
GraphPad

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