title: Brain vascular pericytes following ischemia have multipotential stem cell activity to differentiate into neural and vascular lineage cells.
abstract: Brain vascular pericytes (PCs) are a key component of the blood-brain barrier (BBB)/neurovascular unit, along with neural and endothelial cells. Besides their crucial role in maintaining the BBB, increasing evidence shows that PCs have multipotential stem cell activity. However, their multipotency has not been considered in the pathological brain, such as after an ischemic stroke. Here, we examined whether brain vascular PCs following ischemia (iPCs) have multipotential stem cell activity and differentiate into neural and vascular lineage cells to reconstruct the BBB/neurovascular unit. Using PCs extracted from ischemic regions (iPCs) from mouse brains and human brain PCs cultured under oxygen/glucose deprivation, we show that PCs developed stemness presumably through reprogramming. The iPCs revealed a complex phenotype of angioblasts, in addition to their original mesenchymal properties, and multidifferentiated into cells from both a neural and vascular lineage. These data indicate that under ischemic/hypoxic conditions, PCs can acquire multipotential stem cell activity and can differentiate into major components of the BBB/neurovascular unit. Thus, these findings support the novel concept that iPCs can contribute to both neurogenesis and vasculogenesis at the site of brain injuries.
authors.affiliation: Institute for Advanced Medical Sciences, Nishinomiya, Hyogo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakagomi
authors.affiliation: Department of Genetics, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Kubo
authors.affiliation: Institute for Advanced Medical Sciences, Nishinomiya, Hyogo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Nakano-Doi
authors.affiliation: Institute for Advanced Medical Sciences, Nishinomiya, Hyogo, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Sakuma
authors.affiliation: Institute for Advanced Medical Sciences, Nishinomiya, Hyogo, Japan.|Department of Neurology of Hangzhou First People's Hospital, Hangzhou, People's Republic of China.
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Institute for Advanced Medical Sciences, Nishinomiya, Hyogo, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Narita
authors.affiliation: Institute for Advanced Medical Sciences, Nishinomiya, Hyogo, Japan.|Graduate School of Science and Technology, Kwansei Gakuin University, Sanda, Hyogo, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Kawahara
authors.affiliation: Department of Regenerative Medicine Research, Institute of Biomedical Research and Innovation, Kobe, Hyogo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Taguchi
authors.affiliation: Institute for Advanced Medical Sciences, Nishinomiya, Hyogo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsuyama
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000166:cytology*; D001921:Brain / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D007511:Ischemia / Q000473:pathology; D008297:Male; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000502:physiology; D020286:Pericytes / Q000166:cytology*
keywords: Blood-brain barrier; Ischemia; Neurovascularization; Pericyte; Reprogramming; Stem cell plasticity