Modeling and Targeting Neuroglial Interactions with Human Pluripotent Stem Cell Models

Abstract

Generation of relevant and robust models for neurological disorders is of main importance for both target identification and drug discovery. The non-cell autonomous effects of glial cells on neurons have been described in a broad range of neurodegenerative and neurodevelopmental disorders, pointing to neuroglial interactions as novel alternative targets for therapeutics development. Interestingly, the recent breakthrough discovery of human induced pluripotent stem cells (hiPSCs) has opened a new road for studying neurological and neurodevelopmental disorders “in a dish”. Here, we provide an overview of the generation and modeling of both neuronal and glial cells from human iPSCs and a brief synthesis of recent work investigating neuroglial interactions using hiPSCs in a pathophysiological context.

Neuroprotective Potential of L-Glutamate Transporters in Human Induced Pluripotent Stem Cell-Derived Neural Cells against Excitotoxicity

“…PCC between PSD95 and Syn1 at DIV 63 were low (0.284 ± 0.029, n = 3), indicating that PSD95 is contiguous to Syn1 to be more precise. These changes in localization pattern are consistent with previous reports [15] and indicate the synaptic maturation. These results indicate that glutamatergic synaptic structures were mature at 63 DIV.…”

Asteroid impact: the potential of astrocytes to modulate human neural networks within organoids

“…For over a decade, astrocytes derived from human pluripotent stem cells (hPSCs) have been used as a cellular source to further understand basic neurobiology at the molecular and cellular levels, as well as for disease modeling, as we (Krencik et al, 2011(Krencik et al, , 2015Krencik and Ullian, 2013;Patel et al, 2019) and others (Li and Shi, 2020;Bigarreau et al, 2022;Kumar et al, 2022;Jovanovic et al, 2023) have previously described. However, major caveats remain to be addressed in the traditional methods for astrocyte generation, including the inconsistent choice of differentiation timepoints to conduct studies, cell culture medium components, stress induced by cellular dissociation, use of synthetic substrates that can alter functionality, and lack of neurons and other cell types that contribute intercellular signals for astrocyte physiological maturity.…”

Morphological Characterization of Astrocytes in a Xenograft of Human iPSC-Derived Neural Precursor Cells

“…Трансплантация экспериментальным животным нейронов и астроцитов, полученных из ИПСК человека, помимо разработки методов клеточной терапии, активно используется для изучения патогенеза нейродегенеративных заболеваний и разных аспектов межклеточных взаимодействий [1,2].…”

“…Transplantation of human iPSC-derived neurons and astrocytes to experimental animals is used not only to develop cell therapies, but also to actively study the pathogenesis of neurodegenerative diseases and various aspects of cell-to-cell interactions [ 1 , 2 ].…”