Engineering Brain-Specific Pericytes from Human Pluripotent Stem Cells

Abstract

Pericytes (PCs) are a type of perivascular cells that surround endothelial cells of small blood vessels. In the brain, PCs show heterogeneity depending on their position within the vasculature. As a result, PC interactions with surrounding endothelial cells, astrocytes, and neuron cells play a key role in a wide array of neurovascular functions such as regulating blood-brain barrier (BBB) permeability, cerebral blood flow, and helping to facilitate the clearance of toxic cellular molecules. Therefore, a reliable method of engineering brain-specific PCs from human induced pluripotent stem cells (hiPSCs) is critical in neurodegenerative disease modeling. This review summarizes brain-specific PC differentiation of hiPSCs through mesoderm and neural crest induction. Key signaling pathways (platelet-derived growth factor-B [PDGF-B], transforming growth factor [TGF]-b, and Notch signaling) regulating PC function, PC interactions with adjacent cells, and PC differentiation from hiPSCs are also discussed. Specifically, PDGF-BB-platelet-derived growth factor receptor b signaling promotes PC cell survival, TGF-b signal transduction facilitates PC attachment to endothelial cells, and Notch signaling is critical in vascular development and arterial-venous specification. Furthermore, current challenges facing the use of hiPSC-derived PCs are discussed, and their ongoing uses in neurodegenerative disease modeling are identified. Further investigations into PCs and surrounding cell interactions are needed to characterize the roles of brain PCs in various neurodegenerative disorders.

In Vitro Culture Expansion Shifts the Immune Phenotype of Human Adipose-Derived Mesenchymal Stem Cells

“…Since the target applications of the in vitro expanded hASCs is the treatment of neurological disorders such as stroke, Alzheimer’s disease, or multiple sclerosis, the genes related to brain pericytes, astrocytes, and microglia phenotype were examined ( Supplementary Figures S6B–E ) ( 44 , 56 , 57 ). The more primitive phenotype for brain pericytes and astrocytes was shown in P4 cells compared to P12 cells, and the microglia phenotype was more activated (i.e., pro-inflammatory) in P12 cells.…”

The Glymphatic System: A Novel Therapeutic Target for Stroke Treatment

“…Pericytes are the main mural cells that maintain the BBB integrity at the capillary level ( Jeske et al, 2020 ; Zhang et al, 2020e ). In the brain, astrocytes–pericytes interactions play a key role in regulating BBB permeability and cerebral blood flow and helping to facilitate the clearance of toxic substances.…”

Osthole inhibits proliferation of kainic acid‑activated BV‑2 cells by modulating the Notch signaling pathway

“…in the present study, osthole inhibited the proliferation of Ka-activated BV-2 cells and reduced the release of TNF-α, il-6 and noS2/inoS via the notch signaling pathway, thus serving a neuroprotective role in neuroinflammation. notch signaling serves critical roles in neural stem cell maintenance and neurogenesis and regulation of notch signaling is involved in a number of neurodegenerative diseases and brain disorders (28). Purow et al (29), identified that notch signaling was closely associated with the proliferation of glioma cells.…”

“…Notch signaling serves critical roles in neural stem cell maintenance and neurogenesis and regulation of Notch signaling is involved in a number of neurodegenerative diseases and brain disorders ( 28 ). Purow et al ( 29 ), identified that Notch signaling was closely associated with the proliferation of glioma cells.…”