Induction of Mesoderm and Neural Crest-Derived Pericytes from Human Pluripotent Stem Cells to Study Blood-Brain Barrier Interactions

“…Easy accessibility of pericytes for autologous transplantation highlights their capabilities for future therapeutic studies (Geranmayeh et al, 2019). Since pericyte-like cells derived from induced pluripotent stem cells (iPSC) acquire BBB properties and are incorporated with iPSC-derived endothelial cells, astrocytes and neurons (Faal et al, 2019;Stebbins et al, 2019), iPSC-derived pericytes might also be promising for implantation therapy of AD and other neurological disorders. Pericytes themselves have been shown to acquire stem cell-like and microglial properties after ischemia (Özen et al, 2014;Nakagomi et al, 2015a), which offers another potential therapeutic target for recovery form CNS diseases.…”

Section: Implantation Therapy Application Of Multipotential Stem Celmentioning

confidence: 99%

Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia

Uemura

Maki

Ihara

et al. 2020

Front. Aging Neurosci.

157

112

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Pericytes are unique, multi-functional mural cells localized at the abluminal side of the perivascular space in microvessels. Originally discovered in 19th century, pericytes had drawn less attention until decades ago mainly due to lack of specific markers. Recently, however, a growing body of evidence has revealed that pericytes play various important roles: development and maintenance of blood-brain barrier (BBB), regulation of the neurovascular system (e.g., vascular stability, vessel formation, cerebral blood flow, etc.), trafficking of inflammatory cells, clearance of toxic waste products from the brain, and acquisition of stem cell-like properties. In the neurovascular unit, pericytes perform these functions through coordinated crosstalk with neighboring cells including endothelial, glial, and neuronal cells. Dysfunction of pericytes contribute to a wide variety of diseases that lead to cognitive impairments such as cerebral small vessel disease (SVD), acute stroke, Alzheimer's disease (AD), and other neurological disorders. For instance, in SVDs, pericyte degeneration leads to microvessel instability and demyelination while in stroke, pericyte constriction after ischemia causes a no-reflow phenomenon in brain capillaries. In AD, which shares some common risk factors with vascular dementia, reduction in pericyte coverage and subsequent microvascular impairments are observed in association with white matter attenuation and contribute to impaired cognition. Pericyte loss causes BBB-breakdown, which stagnates amyloid β clearance and the leakage of neurotoxic molecules into the brain parenchyma. In this review, we first summarize the characteristics of brain microvessel pericytes, and their roles in the central nervous system. Then, we focus on how dysfunctional pericytes contribute to the pathogenesis of vascular cognitive impairment including cerebral 'small vessel' and 'large vessel' diseases, as well as AD. Finally, we discuss therapeutic implications for these disorders by targeting pericytes.

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“…Previous studies demonstrated that pericytes and smooth muscle cells in all blood vessels of the face and forebrain are derived from the cephalic (cranial) neural crest 15,16 . Most recently, two studies also verified that forebrain pericyte-like cells (PCs) could be readily differentiated from human pluripotent stem cells (hPSCs) through the cranial neural crest (CNC) stage 17,18 . However, the in vivo functional characteristics and therapeutic potential of hPSC-derived pericyte-like cells still need to be clarified.…”

mentioning

confidence: 97%

Transplantation of hPSC-derived pericyte-like cells promotes functional recovery in ischemic stroke mice

et al. 2020

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Pericytes play essential roles in blood–brain barrier (BBB) integrity and dysfunction or degeneration of pericytes is implicated in a set of neurological disorders although the underlying mechanism remains largely unknown. However, the scarcity of material sources hinders the application of BBB models in vitro for pathophysiological studies. Additionally, whether pericytes can be used to treat neurological disorders remains to be elucidated. Here, we generate pericyte-like cells (PCs) from human pluripotent stem cells (hPSCs) through the intermediate stage of the cranial neural crest (CNC) and reveal that the cranial neural crest-derived pericyte-like cells (hPSC-CNC PCs) express typical pericyte markers including PDGFRβ, CD146, NG2, CD13, Caldesmon, and Vimentin, and display distinct contractile properties, vasculogenic potential and endothelial barrier function. More importantly, when transplanted into a murine model of transient middle cerebral artery occlusion (tMCAO) with BBB disruption, hPSC-CNC PCs efficiently promote neurological functional recovery in tMCAO mice by reconstructing the BBB integrity and preventing of neuronal apoptosis. Our results indicate that hPSC-CNC PCs may represent an ideal cell source for the treatment of BBB dysfunction-related disorders and help to model the human BBB in vitro for the study of the pathogenesis of such neurological diseases.

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Induction of Mesoderm and Neural Crest-Derived Pericytes from Human Pluripotent Stem Cells to Study Blood-Brain Barrier Interactions

Cited by 73 publications

References 30 publications

APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline

APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline

Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia

Transplantation of hPSC-derived pericyte-like cells promotes functional recovery in ischemic stroke mice

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