Modeling Neurovascular Disorders and Therapeutic Outcomes with Human-Induced Pluripotent Stem Cells

Bosworth, Allison M.; Faley, Shannon; Bellan, Leon M.; Lippmann, Ethan S.

doi:10.3389/fbioe.2017.00087

Cited by 27 publications

(22 citation statements)

References 134 publications

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“…Second, iPSCs can be expanded to generate a tremendous amount of starting material for iBEC differentiation and remain relatively consistent in their ability to differentiate into brain endothelial-like cells over many passages [4]. Third, genetic manipulations of iPSCs using gene editing approaches like CRISPR are available and can be used to introduce specific mutations into iBECs for studying gene functions or disease-specific mutations [123]. Fourth, iBECs recapitulate many of the phenotypes present in primary BECs, such as high TEER (> 1000 ohms*cm 2 when differentiated in the presence of retinoic acid), low permeability, and proper expression, localization, and function of TJPs and some BBB transporters.…”

Section: Neuroimmune Studies In Novel Cellular/ Microfabricated Platfmentioning

confidence: 99%

In vitro modeling of blood–brain barrier and interface functions in neuroimmune communication

Erickson

Wilson

Banks

2020

Fluids Barriers CNS

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Neuroimmune communication contributes to both baseline and adaptive physiological functions, as well as disease states. The vascular blood-brain barrier (BBB) and associated cells of the neurovascular unit (NVU) serve as an important interface for immune communication between the brain and periphery through the blood. Immune functions and interactions of the BBB and NVU in this context can be categorized into at least five neuroimmune axes, which include (1) immune modulation of BBB impermeability, (2) immune regulation of BBB transporters, secretions, and other functions, (3) BBB uptake and transport of immunoactive substances, (4) immune cell trafficking, and (5) BBB secretions of immunoactive substances. These axes may act separately or in concert to mediate various aspects of immune signaling at the BBB. Much of what we understand about immune axes has been from work conducted using in vitro BBB models, and recent advances in BBB and NVU modeling highlight the potential of these newer models for improving our understanding of how the brain and immune system communicate. In this review, we discuss how conventional in vitro models of the BBB have improved our understanding of the 5 neuroimmune axes. We further evaluate the existing literature on neuroimmune functions of novel in vitro BBB models, such as those derived from human induced pluripotent stem cells (iPSCs) and discuss their utility in evaluating aspects of neuroimmune communication.

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Section: Neuroimmune Studies In Novel Cellular/ Microfabricated Platfmentioning

confidence: 99%

In vitro modeling of blood–brain barrier and interface functions in neuroimmune communication

Erickson

Wilson

Banks

2020

Fluids Barriers CNS

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“…Neurovascular dysfunction can lead to neural degeneration. 22,59,123,124 The loss of brain PCs can trigger two parallel pathways: 28,125 (i) BBB breakdown, allowing the entrance of circulating plasma proteins, and (ii) chronic hyperfusion and hypoxia (Fig. 5), which can cause the secondary neurodegenerative phenotype.…”

Section: Neural Degenerative Disease Modeling Based On Hipsc-derived Pcsmentioning

confidence: 99%

Engineering Brain-Specific Pericytes from Human Pluripotent Stem Cells

Jeske

Albo

Marzano

et al. 2020

Tissue Engineering Part B: Reviews

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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.

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“…Cerebral complications in preeclampsia are difficult to simulate in in vivo models. [56,57] the hCMEC/d3 cell line has consistently proved to be the most reliable in terms of phenotype and relevance to studying BBB function [58][59][60], whilst in recent years, the use of human pluripotent stem cells (hPSCs) for developing in vitro models of the human BBB appears to be extremely promising [61].…”

Section: Animal Modelsmentioning

confidence: 99%

Investigating Maternal Brain Alterations in Preeclampsia: the Need for a Multidisciplinary Effort

et al. 2019

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Porpuose of Review: To provide insight into the mechanisms underlying cerebral pathophysiology in preeclampsia and to highlight possible methods for evaluation, screening and surveillance of cerebral complications in the condition. Recent Findings: Every 12 minutes, a woman dies as a consequence of preeclampsia with cerebral complications, such as eclampsia, among the most common causes. The incidence of eclampsia has been estimated to vary from one in 100 to one in 2000 deliveries, with the highest incidences in low-income countries. The pathophysiology of eclampsia remains enigmatic. The increased blood pressure cannot be the only underlying cause, since some cases of eclampsia arise without simultaneous hypertension. Evaluation of brain alterations in preeclampsia and eclampsia is challenging and demands a multidisciplinary collaboration, since no single method can accurately and fully describe how preeclampsia affects the brain. Summary: Cerebral complications of preeclampsia are a significant factor in maternal morbidity and mortality worldwide. No single method can accurately describe the full picture of how preeclampsia affects the brain vasculature and parenchyma. We recommend a multinational effort to overcome, not only the issue of limited sample availability, but also, to optimize the quality of research.

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Modeling Neurovascular Disorders and Therapeutic Outcomes with Human-Induced Pluripotent Stem Cells

Cited by 27 publications

References 134 publications

In vitro modeling of blood–brain barrier and interface functions in neuroimmune communication

In vitro modeling of blood–brain barrier and interface functions in neuroimmune communication

Engineering Brain-Specific Pericytes from Human Pluripotent Stem Cells

Investigating Maternal Brain Alterations in Preeclampsia: the Need for a Multidisciplinary Effort

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