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

Sun, Jiaqi; Huang, Yinong; Gong, Jianbin; Wang, Jiancheng; Fan, Yubao; Cai, Jianye; Wang, Yi; Qiu, Yuan; Wei, Yili; Xiong, Chuanfeng; Chen, Jierui; Wang, Bin; Ma, Yuanchen; Hu, Lihua; Chen, Xiaoyong; Zheng, Shuwei; Huang, Weijun; Qin, Ke; Wang, Tao; Li, Xiaoping; Zhang, Wei; Xiang, Andy Peng; Li, Weiqiang

doi:10.1038/s41467-020-19042-y

Cited by 84 publications

(82 citation statements)

References 62 publications

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“…Pericytes have been shown to acquire properties similar to stem cells and microglia after cerebral ischemia, providing another potential therapeutic strategy for recovery from ischemic stroke ( Özen et al, 2014 ; Nakagomi et al, 2015 ). Recently, Sun J. et al (2020) generated pericyte-like cells (PCs) from human pluripotent stem cells (hPSCs). They found the cranial neural crest-derived pericyte-like cells (hPSC-CNC PCs) expressed typical pericyte markers and showed distinct pericyte properties.…”

Section: Introductionmentioning

confidence: 99%

Pericytes for Therapeutic Approaches to Ischemic Stroke

et al. 2021

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Pericytes are perivascular multipotent cells located on capillaries. Although pericytes are discovered in the nineteenth century, recent studies have found that pericytes play an important role in maintaining the blood—brain barrier (BBB) and regulating the neurovascular system. In the neurovascular unit, pericytes perform their functions by coordinating the crosstalk between endothelial, glial, and neuronal cells. Dysfunction of pericytes can lead to a variety of diseases, including stroke and other neurological disorders. Recent studies have suggested that pericytes can serve as a therapeutic target in ischemic stroke. In this review, we first summarize the biology and functions of pericytes in the central nervous system. Then, we focus on the role of dysfunctional pericytes in the pathogenesis of ischemic stroke. Finally, we discuss new therapies for ischemic stroke based on targeting pericytes.

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Section: Introductionmentioning

confidence: 99%

Pericytes for Therapeutic Approaches to Ischemic Stroke

et al. 2021

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“…The blood-brain barrier (BBB) is disrupted after a stroke. The transplanted stem cells can easily cross the BBB to gather in the infarcted brain areas and reconstruct the BBB integrity (Bang et al, 2017 ; Sun et al, 2020 ). Those cells can differentiate into various types of cells forming nervous tissue (e.g., mature neurons, oligodendrocytes, and astrocytes) and release a host of neurotrophic factors and cytokines [e.g., vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), basic fibroblast growth factor (bFGF), nerve growth factor (NGF), insulin-like growth factor 1 (IGF-1)], which could promote neurogenesis to replace injured cells and improve neurological function (Ishibashi et al, 2004 ; Schinköthe et al, 2008 ; Kupcova Skalnikova, 2013 ).…”

Section: Potential Mechanisms Of Stem Cell Therapy For Ischemic Strokmentioning

confidence: 99%

“…Several studies have suggested that a reduction in apoptosis in the ischemic boundary area occurs following cellular therapy that is associated with improved neurological recovery in experimental models (Stonesifer et al, 2017 ; Sun et al, 2020 ). It was reported that the neuroprotective effects of human bone marrow mesenchymal stem cells (hMSCs) against cerebral ischemia could be antagonized by the apoptosis-related Bcl-2 antibody (Zhang et al, 2019 ).…”

Section: Potential Mechanisms Of Stem Cell Therapy For Ischemic Strokmentioning

confidence: 99%

“…When hMSCs were co-cultured with oxygen-glucose deprived (OGD)-injured neurons, they triggered a series of events, including a reduction in rates of apoptosis and necroptosis, downregulation of the necroptosis-related receptor-interacting protein kinase 1 and 3, and deactivation of caspase-3, an enzyme involved in apoptosis (Kong et al, 2017 ). It was proven that stem cells could efficiently promote neurological functional recovery in vivo by preventing neuronal apoptosis (Sun et al, 2020 ). Also, cerebral ischemia was found to promote the release of damage-associated molecular patterns (DAMPs) and matrix metalloproteinases (MMPs), which led to a series of inflammatory responses such as astrocyte and microglia activation, proinflammatory cytokine and chemokine production, and infiltration of leukocytes and neutrophils (Jayaraj et al, 2019 ; Stanzione et al, 2020 ).…”

Section: Potential Mechanisms Of Stem Cell Therapy For Ischemic Strokmentioning

confidence: 99%

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Insight Into the Mechanisms and the Challenges on Stem Cell-Based Therapies for Cerebral Ischemic Stroke

Liu

Reiter

Zhou

et al. 2021

Front. Cell. Neurosci.

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Strokes are the most common types of cerebrovascular disease and remain a major cause of death and disability worldwide. Cerebral ischemic stroke is caused by a reduction in blood flow to the brain. In this disease, two major zones of injury are identified: the lesion core, in which cells rapidly progress toward death, and the ischemic penumbra (surrounding the lesion core), which is defined as hypoperfusion tissue where cells may remain viable and can be repaired. Two methods that are approved by the Food and Drug Administration (FDA) include intravenous thrombolytic therapy and endovascular thrombectomy, however, the narrow therapeutic window poses a limitation, and therefore a low percentage of stroke patients actually receive these treatments. Developments in stem cell therapy have introduced renewed hope to patients with ischemic stroke due to its potential effect for reversing the neurological sequelae. Over the last few decades, animal tests and clinical trials have been used to treat ischemic stroke experimentally with various types of stem cells. However, several technical and ethical challenges must be overcome before stem cells can become a choice for the treatment of stroke. In this review, we summarize the mechanisms, processes, and challenges of using stem cells in stroke treatment. We also discuss new developing trends in this field.

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“…Mature pericytes then become LCBF regulators and by regulating the diameter of capillary vessels and the metabolic and Ca 2+ signals, actively involve the capillary vascular tone ( Cai et al, 2018 ). Pericyte of both endogenous and exogenous sources may interact with NSC or co-transplanted cells to promote flow recovery ( Sun et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Glial Cell-Based Vascular Mechanisms and Transplantation Therapies in Brain Vessel and Neurodegenerative Diseases

Zhao

Wang

Song

et al. 2021

Front. Cell. Neurosci.

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Neurodevelopmental and neurodegenerative diseases (NDDs) with severe neurological/psychiatric symptoms, such as cerebrovascular pathology in AD, CAA, and chronic stroke, have brought greater attention with their incidence and prevalence having markedly increased over the past few years. Causes of the significant neuropathologies, especially those observed in neurological diseases in the CNS, are commonly believed to involve multiple factors such as an age, a total environment, genetics, and an immunity contributing to their progression, neuronal, and vascular injuries. We primarily focused on the studies of glial involvement/dysfunction in part with the blood-brain barrier (BBB) and the neurovascular unit (NVU) changes, and the vascular mechanisms, which have been both suggested as critical roles in chronic stroke and many other NDDs. It has been noted that glial cells including astrocytes (which outnumber other cell types in the CNS) essentially contribute more to the BBB integrity, extracellular homeostasis, neurotransmitter release, regulation of neurogenic niches in response to neuroinflammatory stimulus, and synaptic plasticity. In a recent study for NDDs utilizing cellular and molecular biology and genetic and pharmacological tools, the role of reactive astrocytes (RACs) and gliosis was demonstrated, able to trigger pathophysiological/psychopathological detrimental changes during the disease progression. We speculate, in particular, the BBB, the NVU, and changes of the astrocytes (potentially different populations from the RACs) not only interfere with neuronal development and synaptogenesis, but also generate oxidative damages, contribute to beta-amyloid clearances and disrupted vasculature, as well as lead to neuroinflammatory disorders. During the past several decades, stem cell therapy has been investigated with a research focus to target related neuro-/vascular pathologies (cell replacement and repair) and neurological/psychiatric symptoms (paracrine protection and homeostasis). Evidence shows that transplantation of neurogenic or vasculogenic cells could be achieved to pursue differentiation and maturation within the diseased brains as expected. It would be hoped that, via regulating functions of astrocytes, astrocytic involvement, and modulation of the BBB, the NVU and astrocytes should be among major targets for therapeutics against NDDs pathogenesis by drug and cell-based therapies. The non-invasive strategies in combination with stem cell transplantation such as the well-tested intranasal deliveries for drug and stem cells by our and many other groups show great translational potentials in NDDs. Neuroimaging and clinically relevant analyzing tools need to be evaluated in various NDDs brains.

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

Cited by 84 publications

References 62 publications

Pericytes for Therapeutic Approaches to Ischemic Stroke

Pericytes for Therapeutic Approaches to Ischemic Stroke

Insight Into the Mechanisms and the Challenges on Stem Cell-Based Therapies for Cerebral Ischemic Stroke

Glial Cell-Based Vascular Mechanisms and Transplantation Therapies in Brain Vessel and Neurodegenerative Diseases

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