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

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 formation of the neuro-angiogenic niche.

Zika virus infection leads to mitochondrial failure, oxidative stress and DNA damage in human iPSC-derived astrocytes

“…Here we used human iPSC-derived brain cells to investigate which cell types are most infected by ZIKV. Neural stem cells and neurons were generated as previously described 38,39 . Astrocyte differentiation followed the protocol described by Yan et al, 2013 39 and exhibited the main astrocytic markers ( Supplementary Material -Fig.…”

“…GM23279A iPSC line was obtained commercially from Coriell Institute Biobank; CF2 and CF1 lines were generated from fibroblasts, and C15 were generated from urine cells. GM23279A, CF1 and CF2 cell lines were previously published in Casas et al 38 . C15 cell line was published in Trindade et al 53 .…”

Twist1 promotes astrocytoma development by stimulating vasculogenic mimicry

“…Angiogenesis is also a prominent feature of astrocytoma, and is associated with its malignant progression (23,24). Glioblastoma is the highest grade of astrocytoma (WHOIV) and is the most vasculogenic malignancy (25,26). In order to increase the effectiveness of clinical treatment, further investigation into the molecular mechanism of astrocytoma angiogenesis is required.…”

Short and long TNF‐alpha exposure recapitulates canonical astrogliosis events in human‐induced pluripotent stem cells‐derived astrocytes

“…NSC were obtained according to a protocol described previously (Yan et al, ). These cell lines were used in other studies from our research group (Casas et al, ; Garcez et al, ; Ledur et al, 2020). One cell line was obtained from a female subject (Subject 1—available at Coriell Institute Biobank with the name GM23279A) and the other three from subjects whose cells were reprogrammed at the D'Or Institute for Research and Education (Subjects 2, 3, and 4).…”