Bioengineered perfused human brain microvascular networks enhance neural progenitor cell survival, neurogenesis, and maturation

Abstract

Neural progenitor cells (NPCs) have the capability to self-renew and differentiate into neurons and glial cells. In the adult brain, NPCs are found near brain microvascular networks (BMVNs) in specialized microenvironments called the neurovascular niche (NVN). Although several in vitro NVN models have been previously reported, most do not properly recapitulate the intimate cellular interactions between NPCs and perfused brain microvessels. Here, we developed perfused BMVNs composed of primary human brain endothelial cells, pericytes, and astrocytes within microfluidic devices. When induced pluripotent stem cell–derived NPCs were introduced into BMVNs, we found that NPC survival, neurogenesis, and maturation were enhanced. The application of flow during BMVN coculture was also beneficial for neuron differentiation. Collectively, our work highlighted the important role of BMVNs and flow in NPC self-renewal and neurogenesis, as well as demonstrated our model’s potential to study the biological and physical interactions of human NVN in vitro.

A systematic review of the neuropathology and memory decline induced by monosodium glutamate in the Alzheimer’s disease-like animal model

“…The hallmark pathologies of this illness, including amyloid-β buildup, tau hyperphosphorylation, and neuronal death, are brought on by increased intracellular calcium ( Jadiya et al, 2023 ; Mahaman et al, 2023 ). Thus, an increase in the amyloid and Ki-67 protein expression along with the proliferation of astrocyte nuclei and calcium signaling S-100 in the hippocampus regulates the number of processes related to Alzheimer’s disease ( Winkelman and Dai, 2023 ).…”

Advances in the knowledge and therapeutics of schizophrenia, major depression disorder, and bipolar disorder from human brain organoid research

“…In this assay, cells are cultured in micro-channels subjected to controlled fluid flow within a microfluidic device that is provided with biosensors to monitor biomarkers secreted by the organoids ( 42 , 43 ). In addition to detect modifications induced by selected drug treatments, this assay enables to explore interactions between distinct organoids growing within channels interconnected together (“multiorgans microdevice”) or to generate a network of microvessels by adding growing vascular progenitors in connection with the organoid ( 44 ). Over-all, the organ-on-chip technology is a fast-moving field of research, and we could anticipate, that distinct types of these organ chip models will be manufactured and standardized in the next future [see ( 42 , 45 )].…”