Single Cell Analysis in Vascular Biology

Chavkin, Nicholas W.; Hirschi, Karen K.

doi:10.3389/fcvm.2020.00042

Cited by 59 publications

(46 citation statements)

References 169 publications

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“…Endothelial cell injury and systemic toxins or inflammation can cause endothelial activation, adhesion of leukocytes, platelet thrombus formation, and concomitant microvascular dysfunction (discussed in detail above under Thrombotic Microangiopathy). Single-cell RNA sequencing data is now opening new perspectives on the diversity of brain endothelial cells, but data on changes in the endothelial transcriptome in inflammatory disease are just emerging (170)(171)(172). For example, a novel group of interferon-responsive brain endothelial cells was discovered by scRNAseq, whose functional role has yet to be studied (173).…”

Section: Brain Microvascular Endothelial Cellsmentioning

confidence: 99%

Cytokines in CAR T Cell–Associated Neurotoxicity

et al. 2020

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Chimeric antigen receptor (CAR) T cells provide new therapeutic options for patients with relapsed/refractory hematologic malignancies. However, neurotoxicity is a frequent, and potentially fatal, complication. The spectrum of manifestations ranges from delirium and language dysfunction to seizures, coma, and fatal cerebral edema. This novel syndrome has been designated immune effector cell–associated neurotoxicity syndrome (ICANS). In this review, we draw an arc from our current understanding of how systemic and potentially local cytokine release act on the CNS, toward possible preventive and therapeutic approaches. We systematically review reported correlations of secreted inflammatory mediators in the serum/plasma and cerebrospinal fluid with the risk of ICANS in patients receiving CAR T cell therapy. Possible pathophysiologic impacts on the CNS are covered in detail for the most promising candidate cytokines, including IL-1, IL-6, IL-15, and GM-CSF. To provide insight into possible final common pathways of CNS inflammation, we place ICANS into the context of other systemic inflammatory conditions that are associated with neurologic dysfunction, including sepsis-associated encephalopathy, cerebral malaria, thrombotic microangiopathy, CNS infections, and hepatic encephalopathy. We then review in detail what is known about systemic cytokine interaction with components of the neurovascular unit, including endothelial cells, pericytes, and astrocytes, and how microglia and neurons respond to systemic inflammatory challenges. Current therapeutic approaches, including corticosteroids and blockade of IL-1 and IL-6 signaling, are reviewed in the context of what is known about the role of cytokines in ICANS. Throughout, we point out gaps in knowledge and possible new approaches for the investigation of the mechanism, prevention, and treatment of ICANS.

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Section: Brain Microvascular Endothelial Cellsmentioning

confidence: 99%

Cytokines in CAR T Cell–Associated Neurotoxicity

et al. 2020

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“…With the advent of scRNAseq, it is now possible to discover signatures of sprouting and proliferative cells in virtually any developmental context and organ. Even though the field has initially focused in scRNAseq analysis of wildtype adult organ vessels [7,169,[301][302][303], the number of different ongoing scRNAseq studies and developmental contexts analyzed is rapidly increasing and already some studies provided an unprecedented level of cellular resolution on the molecular mechanisms driving developmental angiogenesis [285,304]. The combination of targeted functional genetics with scOMICS will certainly change our understanding of vascular cell heterogeneity and the process of angiogenesis.…”

Section: Resultsmentioning

confidence: 99%

Endothelial sprouting, proliferation, or senescence: tipping the balance from physiology to pathology

Mühleder

Fernández-Chacón

García-González

et al. 2020

Cell. Mol. Life Sci.

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Therapeutic modulation of vascular cell proliferation and migration is essential for the effective inhibition of angiogenesis in cancer or its induction in cardiovascular disease. The general view is that an increase in vascular growth factor levels or mitogenic stimulation is beneficial for angiogenesis, since it leads to an increase in both endothelial proliferation and sprouting. However, several recent studies showed that an increase in mitogenic stimuli can also lead to the arrest of angiogenesis. This is due to the existence of intrinsic signaling feedback loops and cell cycle checkpoints that work in synchrony to maintain a balance between endothelial proliferation and sprouting. This balance is tightly and effectively regulated during tissue growth and is often deregulated or impaired in disease. Most therapeutic strategies used so far to promote vascular growth simply increase mitogenic stimuli, without taking into account its deleterious effects on this balance and on vascular cells. Here, we review the main findings on the mechanisms controlling physiological vascular sprouting, proliferation, and senescence and how those mechanisms are often deregulated in acquired or congenital cardiovascular disease leading to a diverse range of pathologies. We also discuss alternative approaches to increase the effectiveness of pro-angiogenic therapies in cardiovascular regenerative medicine.

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“…In the process of angiogenesis, progenitor cells gradually acquire markers of ECs phenotype and then are directionally differentiated into arterial, venous and capillary ECs [ 188 , 189 ]. ECs in different areas are heterogeneous cell populations [ 190 , 191 ], and each of them has unique molecular markers [ 192 ], but this molecular marker can be altered [ 193 ]. While tissue microenvironment may play an important role in regulating endothelial heterogeneity [ 194 , 195 ].…”

Section: Heterogeneity Of Vascular Endotheliummentioning

confidence: 99%

Selection of different endothelialization modes and different seed cells for tissue-engineered vascular graft

Cai

Liao

Xue

et al. 2021

Bioactive Materials

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Tissue-engineered vascular grafts (TEVGs) have enormous potential for vascular replacement therapy. However, thrombosis and intimal hyperplasia are important problems associated with TEVGs especially small diameter TEVGs (<6 mm) after transplantation. Endothelialization of TEVGs is a key point to prevent thrombosis. Here, we discuss different types of endothelialization and different seed cells of tissue-engineered vascular grafts. Meanwhile, endothelial heterogeneity is also discussed. Based on it, we provide a new perspective for selecting suitable types of endothelialization and suitable seed cells to improve the long-term patency rate of tissue-engineered vascular grafts with different diameters and lengths.

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Single Cell Analysis in Vascular Biology

Cited by 59 publications

References 169 publications

Cytokines in CAR T Cell–Associated Neurotoxicity

Cytokines in CAR T Cell–Associated Neurotoxicity

Endothelial sprouting, proliferation, or senescence: tipping the balance from physiology to pathology

Selection of different endothelialization modes and different seed cells for tissue-engineered vascular graft

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