Do Vascular Pericytes Contribute to Neurovasculogenesis in the Central Nervous System as Multipotent Vascular Stem Cells?

Nakagomi, Takayuki; Nakano‐Doi, Akiko; Kawamura, Miki; Matsuyama, Tomohiro

doi:10.1089/scd.2015.0039

Cited by 37 publications

(27 citation statements)

References 131 publications

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“…Central nervous system pericytes have been proposed to function as the major contributor to fibrotic scarring (Goritz et al, 2011), as progenitors of microglia (Sakuma et al, 2016), and as progenitors of neurons, astrocytes and oligodendrocytes (Dore-Duffy et al, 2006; Nakagomi et al, 2015). However, our studies revealed that brain pericytes maintained their identity and did not transdifferentiate into other lineages during aging (Figure 4).…”

Section: Resultsmentioning

confidence: 99%

Pericytes of Multiple Organs Do Not Behave as Mesenchymal Stem Cells In Vivo

et al. 2017

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Summary Pericytes are widely believed to function as mesenchymal stem cells (MSCs) -multipotent tissue-resident progenitors with great potential for regenerative medicine. Cultured pericytes isolated from distinct tissues can differentiate into multiple cell types in vitro, or following transplantation in vivo. However, the cell fate plasticity of endogenous pericytes in vivo remains unclear. Here, we show that the transcription factor Tbx18 selectively marks pericytes and vascular smooth muscle cells in multiple organs of adult mouse. FACS-purified Tbx18-expressing cells behaved as MSCs in vitro. However, lineage-tracing experiments using an inducible Tbx18-CreERT2 line revealed that pericytes and vascular smooth muscle cells maintained their identity in aging and diverse pathological settings, and did not significantly contribute to other cell lineages. These results challenge the current view of endogenous pericytes as multipotent tissue-resident progenitors, and suggest that the plasticity observed in vitro or following transplantation in vivo arises from artificial cell manipulations ex vivo.

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Section: Resultsmentioning

confidence: 99%

Pericytes of Multiple Organs Do Not Behave as Mesenchymal Stem Cells In Vivo

et al. 2017

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“…Microglia signals likely work with other niche molecules known to influence NSC behavior such as those from the vasculature [42,43,[59][60][61], CSF [20,62,63], and ependymal cells [64]. Numerous reports suggest that activation of microglia can be proneurogenic or antineurogenic in the V-SVZ depending on the context.…”

Section: Discussionmentioning

confidence: 99%

Neurogenic Niche Microglia Undergo Positional Remodeling and Progressive Activation Contributing to Age-Associated Reductions in Neurogenesis

Fonseca

Mahesula

Apple

et al. 2016

Stem Cells and Development

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Neural stem cells (NSCs) exist throughout life in the ventricular-subventricular zone (V-SVZ) of the mammalian forebrain. During aging NSC function is diminished through an unclear mechanism. In this study, we establish microglia, the immune cells of the brain, as integral niche cells within the V-SVZ that undergo ageassociated repositioning in the V-SVZ. Microglia become activated early before NSC deficits during aging resulting in an antineurogenic microenvironment due to increased inflammatory cytokine secretion. These ageassociated changes were not observed in non-neurogenic brain regions, suggesting V-SVZ microglia are specialized. Using a sustained inflammatory model in young adult mice, we induced microglia activation and inflammation that was accompanied by reduced NSC proliferation in the V-SVZ. Furthermore, in vitro studies revealed secreted factors from activated microglia reduced proliferation and neuron production compared to secreted factors from resting microglia. Our results suggest that age-associated chronic inflammation contributes to declines in NSC function within the aging neurogenic niche.

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“…234 In addition, pericytes may differentiate into other cell types and thus may be important for CNS renewal. 235 …”

Section: Part II Neurovascular Injury and Repair After Ischemic Strokementioning

confidence: 99%

Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke

Silva

Chen

et al. 2017

Circulation Research

312

237

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The consequences of cerebrovascular disease are among the leading health issues worldwide. Large and small cerebral vessel disease can trigger stroke and contribute to the vascular component of other forms of neurological dysfunction and degeneration. Both forms of vascular disease are driven by diverse risk factors, with hypertension as the leading contributor. Despite the importance of neurovascular disease and subsequent injury following ischemic events, fundamental knowledge in these areas lag behind our current understanding of neuroprotection and vascular biology in general. The goal of this review is to address select key structural and functional changes in the vasculature that promote hypoperfusion and ischemia, while also affecting the extent of injury and effectiveness of therapy. In addition, as damage to the blood-brain barrier (BBB) is one of the major consequences of ischemia, we discuss cellular and molecular mechanisms underlying ischemia-induced changes in BBB integrity and function, including alterations in endothelial cells and the contribution of pericytes, immune cells, and matrix metalloproteinases. Identification of cell types, pathways, and molecules that control vascular changes before and after ischemia may result in novel approaches to slow the progression of cerebrovascular disease and lessen both the frequency and impact of ischemic events.

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Do Vascular Pericytes Contribute to Neurovasculogenesis in the Central Nervous System as Multipotent Vascular Stem Cells?

Cited by 37 publications

References 131 publications

Pericytes of Multiple Organs Do Not Behave as Mesenchymal Stem Cells In Vivo

Pericytes of Multiple Organs Do Not Behave as Mesenchymal Stem Cells In Vivo

Neurogenic Niche Microglia Undergo Positional Remodeling and Progressive Activation Contributing to Age-Associated Reductions in Neurogenesis

Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke

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