Abstract
Human cerebral organoids derived from induced pluripotent stem cells (iPSCs) provide novel tools for recapitulating the cytoarchitecture of the human brain and for studying biological mechanisms of neurological disorders. However, the heterotypic interactions of neurovascular units, composed of neurons, pericytes (i.e., the tissue resident mesenchymal stromal cells), astrocytes, and brain microvascular endothelial cells, in brain-like tissues are less investigated. In addition, most cortical organoids lack a microglia component, the resident immune cells in the brain. Impairment of the blood-brain barrier caused by improper crosstalk between neural cells and vascular cells is associated with many neurodegenerative disorders. Mesenchymal stem cells (MSCs), with a phenotype overlapping with pericytes, have promotion effects on neurogenesis and angiogenesis, which are mainly attributed to secreted growth factors and extracellular matrices. As the innate macrophages of the central nervous system, microglia regulate neuronal activities and promote neuronal differentiation by secreting neurotrophic factors and pro-/anti-inflammatory molecules. Neuronal-microglia interactions mediated by chemokines signaling can be modulated in vitro for recapitulating microglial activities during neurodegenerative disease progression. In this review, we discussed the cellular interactions and the physiological roles of neural cells with other cell types including endothelial cells and microglia based on iPSC models. The therapeutic roles of MSCs in treating neural degeneration and pathological roles of microglia in neurodegenerative disease progression were also discussed.
Highlights
Recent human-induced pluripotent stem cell technology has provided a remarkable alternative for human in vitro models through the derivation of lineage-specific cells from patients with diverse neurological diseases
Our study showed that Mesenchymal stem cells (MSCs) promoted dorsal cortical spheroid formation [50]
A novel human blood–brain barrier (BBB) micro-physiological system consisting of a 3D printed electrospun poly(lactic-co-glycolic) acid nanofibrous mesh, and a bilayer co-culture of human astrocytes and endothelial cells derived from human-induced pluripotent stem cell (hiPSC) [66]
Summary
Recent human-induced pluripotent stem cell (hiPSC) technology has provided a remarkable alternative for human in vitro models through the derivation of lineage-specific cells from patients with diverse neurological diseases. 24 recent study reported a generalized method to form organ buds of different types of tissues (e.g., liver, kidney, a promising platform disease modeling as cells well as a transplantation entity to regenerate functional tissue brain etc.) in vivo usingformesenchymal stem (MSCs), endothelial cells, and hiPSC-derived organs. Organ buds self-organized into multiple functional and vascularized our lab investigated the vascularization of cortical organoids in vitro through tri-culture of organs such as liver or kidney after the transplantation [16,17] This approach mixed the iNPCs, iECs, and human MSCs and investigated heterotypic neural-vascular-mesenchymal cells of different types and the cell organization and tissue structure are uncontrolled.
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