Brain Vascular Pericytes Following Ischemia Have Multipotential Stem Cell Activity to Differentiate Into Neural and Vascular Lineage Cells

Nakagomi, Takayuki; Kubo, Shuji; Nakano‐Doi, Akiko; Sakuma, Rika; Lu, Shan; Narita, Aya; Kawahara, Maiko; Taguchi, Akihiko; Matsuyama, Tomohiro

doi:10.1002/stem.1977

“…However, reprogramming has been reported to cause adult brain pericytes to become non-pericytic lineages, such as neuronal lineages (10). In support of this notion, we showed that adult brain pericytes, which do not possess stem cell activity under normal conditions, reacquired stemness in response to ischemia, presumably through cellular reprogramming by mesenchymal-epithelial transition (11,12). We also showed that PDGFRβ + cells isolated from ischemic areas, including the leptomeninges, have a multipotent stem cell activity that gives rise to neuronal cells (11,12).…”

supporting

confidence: 79%

“…In support of this notion, we showed that adult brain pericytes, which do not possess stem cell activity under normal conditions, reacquired stemness in response to ischemia, presumably through cellular reprogramming by mesenchymal-epithelial transition (11,12). We also showed that PDGFRβ + cells isolated from ischemic areas, including the leptomeninges, have a multipotent stem cell activity that gives rise to neuronal cells (11,12). Therefore, we proposed that brain pericytes localized along the leptomeninges to cortical parenchyma are likely the origin of leptomeningeal stem cells.…”

supporting

confidence: 60%

“…O f n o t e , u s i n g s i n g l e -c e l l transcriptomics, they also showed that leptomeningeal PDGFRβ + cells generate various types of clusters that exhibited features of pericytic/fibroblastic, endothelial, and microglial lineages in addition to radial glia-like lineages. However, we recently showed that PDGFRβ + pericytes isolated from post-stroke areas, including the leptomeninges, exhibited multipotent stem cell activity and that they give rise to not only neural (e.g., neurons) but also vascular lineages (e.g., endothelial cells and microglia) (11,12 (5,6,19,20). Thus, the leptomeninges should become a new target for treating CNS developmental disorders and diseases.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Leptomeninges: a novel stem cell niche with neurogenic potential

Nakagomi¹,

Matsuyama²

2017

Stem Cell Investig.

Self Cite

View full text Add to dashboard Cite

“…After acute ischemia, proliferation of these, and other, progenitor cells in the CNS is enhanced [88,136,137], and, similarly, shorter pulses of ischemia to induce preconditioning effects also result in the proliferation of progenitors [137,138], with an increase of up to 4-fold observed after preconditioning in one study [137]. Interestingly, when proliferation was attenuated by administration of methylazoxymethanol acetate or ganciclovir, the preconditioning effect of a short ischemic event (15 min MCAO) was abolished [137]. These data suggest that the proliferation of progenitors is an effector of IPC-mediated neuroprotection.…”

Section: Progenitor Cellsmentioning

confidence: 99%

Neuroimmune Response in Ischemic Preconditioning

McDonough

¹

,

Weinstein

²

2016

View full text Add to dashboard Cite

Ischemic preconditioning (IPC) is a robust neuroprotective phenomenon in which a brief period of cerebral ischemia confers transient tolerance to subsequent ischemic challenge. Research on IPC has implicated cellular, molecular, and systemic elements of the immune response in this phenomenon. Potent molecular mediators of IPC include innate immune signaling pathways such as Toll-like receptors and type 1 interferons. Brain ischemia results in release of proand anti-inflammatory cytokines and chemokines that orchestrate the neuroinflammtory response, resolution of inflammation, and transition to neurological recovery and regeneration. Cellular mediators of IPC include microglia, the resident central nervous system immune cells, astrocytes, and neurons. All of these cell types engage in cross-talk with each other using a multitude of signaling pathways that modulate activation/ suppression of each of the other cell types in response to ischemia. As the postischemic neuroimmune response evolves over time there is a shift in function toward provision of trophic support and neuroprotection. Peripheral immune cells infiltrate the central nervous system en masse after stroke and are largely detrimental, with a few subtypes having beneficial, protective effects, though the role of these immune cells in IPC is largely unknown. The role of neural progenitor cells in IPC-mediated neuroprotection is another active area of investigation as is the role of microglial proliferation in this setting. A mechanistic understanding of these molecular and cellular mediators of IPC may not only facilitate more effective direct application of IPC to specific clinical scenarios, but also, more broadly, reveal novel targets for therapeutic intervention in stroke.

show abstract

“…Although some of these proliferative cells in the hippocampus may differentiate into NeuN + cells [138], the identity of other proliferating cells in different regions of the brain has not been fully determined, but there is evidence that microvascular pericytes proliferate in response to ischemia [139], as do reactive astrocytes [140]. We have observed in a model of IPC (15 min MCAO) that the number of microglia substantially and significantly increases in the ipsilateral hemisphere of a preconditioned mouse (Fig.…”

Section: Progenitor Cellsmentioning

confidence: 89%

Correction to: Neuroimmune Response in Ischemic Preconditioning

McDonough

¹

,

Weinstein

²

2018

View full text Add to dashboard Cite

Ischemic preconditioning (IPC) is a robust neuroprotective phenomenon in which a brief period of cerebral ischemia confers transient tolerance to subsequent ischemic challenge. Research on IPC has implicated cellular, molecular, and systemic elements of the immune response in this phenomenon. Potent molecular mediators of IPC include innate immune signaling pathways such as Tolllike receptors and type 1 interferons. Brain ischemia results in release of pro-and anti-inflammatory cytokines and chemokines that orchestrate the neuroinflammatory response, resolution of inflammation, and transition to neurological recovery and regeneration. Cellular mediators of IPC include microglia, the resident central nervous system immune cells, astrocytes, and neurons. All of these cell types engage in cross-talk with each other using a multitude of signaling pathways that modulate activation/ suppression of each of the other cell types in response to ischemia. As the postischemic neuroimmune response evolves over time there is a shift in function toward provision of trophic support and neuroprotection. Peripheral immune cells infiltrate the central nervous system en masse after stroke and are largely detrimental, with a few subtypes having beneficial, protective effects, though the role of these immune cells in IPC is largely unknown. The role of neural progenitor cells in IPC-mediated neuroprotection is another active area of investigation as is the role of microglial proliferation in this setting. A mechanistic understanding of these molecular and cellular mediators of IPC may not only facilitate more effective direct application of IPC to specific clinical scenarios, but also, more broadly, reveal novel targets for therapeutic intervention in stroke. Keywords PreconditioningIschemic preconditioning (IPC) is an experimental phenomenon in which a brief period of ischemia confers robust neuroprotection against subsequent ischemic events [1-3]. It is important to note that preconditioning does not reduce the incidence of stroke, but rather ameliorates the pathophysiologic response to cerebral ischemia and results in a smaller infarct volume and improved poststroke recovery [4][5][6]. Clinical studies suggest that patients with stroke who suffered a recent prior transient ischemic attack have better outcomes than those who did not, implying that a human correlate to experimental IPC exists [7,8]. Elucidating the mechanisms of IPC is considered a critical challenge in stroke research [9,10]. Recent literature has implicated innate immune pathways, including Toll-like receptors (TLRs) [11,12] and type 1 interferon (IFN) signaling [5,11,13] in IPC-mediated protection.Due to a technical error in the production process, the earlier version of this article contained numerous errors in the reference numbering. We are reprinting the entire article in the correction for readabilityThe online version of the original article can be found at https://doi

show abstract

Brain Vascular Pericytes Following Ischemia Have Multipotential Stem Cell Activity to Differentiate Into Neural and Vascular Lineage Cells

Cited by 203 publications

References 65 publications

Leptomeninges: a novel stem cell niche with neurogenic potential

Leptomeninges: a novel stem cell niche with neurogenic potential

Neuroimmune Response in Ischemic Preconditioning

Correction to: Neuroimmune Response in Ischemic Preconditioning

Contact Info

Product

Resources

About