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Journal of the Formosan Medical... Mar 2024Studies have highlighted the significant involvement of kidney pericytes in renal fibrosis. Kidney pericytes, classified as interstitial mesenchymal cells, are... (Review)
Review
Studies have highlighted the significant involvement of kidney pericytes in renal fibrosis. Kidney pericytes, classified as interstitial mesenchymal cells, are extensively branched, collagen-producing cells that closely interact with endothelial cells. This article aims to provide an overview of the recent advancements in understanding the physiological functions of pericytes and their roles in kidney diseases. In a healthy kidney, pericytes have essential physiological function in angiogenesis, erythropoietin (EPO) production, and the regulation of renal blood flow. Nevertheless, pericyte-myofibroblast transition has been identified as the primary cause of disease progression in acute kidney injury (AKI)-to-chronic kidney disease (CKD) continuum. Our recent research has demonstrated that hypoxia-inducible factor-2α (HIF-2α) regulates erythropoietin production in pericytes. However, this production is repressed by EPO gene hypermethylation and HIF-2α downregulation which were induced by transforming growth factor-β1-activated DNA methyltransferase and activin receptor-like kinase-5 signaling pathway during renal fibrosis, respectively. Additionally, AKI induces epigenetic modifications in pericytes, rendering them more prone to extracellular matrix production, cell migration and proliferation, thereby contributing to subsequent capillary rarefaction and renal fibrosis. Further investigation into the specific functions and roles of different subpopulations of pericytes may contribute for the development of targeted therapies aimed at attenuating kidney disease and mitigating their adverse effects.
Topics: Humans; Pericytes; Endothelial Cells; Kidney; Kidney Diseases; Renal Insufficiency, Chronic; Erythropoietin; Acute Kidney Injury; Fibrosis; Basic Helix-Loop-Helix Transcription Factors
PubMed: 37586973
DOI: 10.1016/j.jfma.2023.08.002 -
Cells Apr 2022Brain tissue contains the highest number of perivascular pericytes compared to other organs. Pericytes are known to regulate brain perfusion and to play an important... (Review)
Review
Brain tissue contains the highest number of perivascular pericytes compared to other organs. Pericytes are known to regulate brain perfusion and to play an important role within the neurovascular unit (NVU). The high phenotypic and functional plasticity of pericytes make this cell type a prime candidate to aid physiological adaptations but also propose pericytes as important modulators in diverse pathologies in the brain. This review highlights known phenotypes of pericytes in the brain, discusses the diverse markers for brain pericytes, and reviews current in vitro and in vivo experimental models to study pericyte function. Our current knowledge of pericyte phenotypes as it relates to metastatic growth patterns in breast cancer brain metastasis is presented as an example for the crosstalk between pericytes, endothelial cells, and metastatic cells. Future challenges lie in establishing methods for real-time monitoring of pericyte crosstalk to understand causal events in the brain metastatic process.
Topics: Brain; Brain Neoplasms; Breast Neoplasms; Endothelial Cells; Female; Humans; Pericytes
PubMed: 35455945
DOI: 10.3390/cells11081263 -
The American Journal of Pathology Nov 2021Prevalence of dementia continues to increase because of the aging population and limited treatment options. Cerebral small vessel disease and Alzheimer disease are the... (Review)
Review
Prevalence of dementia continues to increase because of the aging population and limited treatment options. Cerebral small vessel disease and Alzheimer disease are the two most common causes of dementia with vascular dysfunction being a large component of both their pathophysiologies. The neurogliovascular unit, in particular the blood-brain barrier (BBB), is required for maintaining brain homeostasis. A complex interaction exists among the endothelial cells, which line the blood vessels and pericytes, which surround them in the neurogliovascular unit. Disruption of the BBB in dementia precipitates cognitive decline. This review highlights how dysfunction of the endothelial-pericyte crosstalk contributes to dementia, and focuses on cerebral small vessel disease and Alzheimer disease. It also examines loss of pericyte coverage and subsequent downstream changes. Furthermore, it examines how disruption of the intimate crosstalk between endothelial cells and pericytes leads to alterations in cerebral blood flow, transcription, neuroinflammation, and transcytosis, contributing to breakdown of the BBB. Finally, this review illustrates how cumulation of loss of endothelial-pericyte crosstalk is a major driving force in dementia pathology.
Topics: Alzheimer Disease; Animals; Blood-Brain Barrier; Brain; Cell Communication; Cerebral Small Vessel Diseases; Dementia; Endothelial Cells; Humans; Pericytes
PubMed: 34329605
DOI: 10.1016/j.ajpath.2021.07.003 -
Frontiers in Bioscience (Landmark... Apr 2024Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder characterized by aberrant amyloid precursor protein (APP) cleavage, pathological... (Review)
Review
Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder characterized by aberrant amyloid precursor protein (APP) cleavage, pathological aggregations of beta-amyloid (Aβ) that make up Aβ plaques and hyperphosphorylation of Tau that makes up neurofibrillary tangles (NFTs). Although progress has been made in research on AD, the fundamental causes of this disease have not been fully elucidated. Recent studies have shown that vascular dysfunction especially the loss of pericytes plays a significant role in the onset of AD. Pericytes play a variety of important roles in the nervous system including the regulation of the cerebral blood flow (CBF), the formation and maintenance of the blood-brain barrier (BBB), angiogenesis, and the clearance of toxic substances from the brain. Pericytes participate in the transport of Aβ through various receptors, and Aβ acts on pericytes to cause them to constrict, detach, and die. The loss of pericytes elevates the levels of Aβ1-40 and Aβ1-42 by disrupting the integrity of the BBB and reducing the clearance of soluble Aβ from the brain interstitial fluid. The aggravated deposition of Aβ further exacerbates pericyte dysfunction, forming a vicious cycle. The combined influence of these factors eventually results in the loss of neurons and cognitive decline. Further exploration of the interactions between pericytes and Aβ is beneficial for understanding AD and could lead to the identification of new therapeutic targets for the prevention and treatment of AD. In this review, we explore the characterization of pericytes, interactions between pericytes and other cells in the neurovascular unit (NVU), and the physiological functions of pericytes and dysfunctions in AD. This review discusses the interactions between pericytes and Aβ, as well as current and further strategies for preventing or treating AD targeting pericytes.
Topics: Pericytes; Alzheimer Disease; Humans; Amyloid beta-Peptides; Blood-Brain Barrier; Animals; Brain
PubMed: 38682184
DOI: 10.31083/j.fbl2904136 -
Current Opinion in Immunology Jun 2020The mesenchymal microenvironment is increasingly recognized as a major player in immunity. Here we focus on mesenchymal cells located within or in proximity to the blood... (Review)
Review
The mesenchymal microenvironment is increasingly recognized as a major player in immunity. Here we focus on mesenchymal cells located within or in proximity to the blood vessels wall, which include pericytes, adventitial fibroblasts and mesenchymal stromal cells. We discuss recent evidence that these cells play a role in tissue homeostasis, immunity and inflammatory pathologies by multiple mechanisms, including vascular modulation, leucocyte migration, activation or survival in the perivascular space and differentiation into specialized 'effector' mesenchymal cells essential for tissue repair and immunity, such as myofibroblasts and lymphoid stromal cells. When dysregulated, these responses contribute to inflammatory and fibrotic diseases.
Topics: Cell Differentiation; Fibroblasts; Humans; Mesenchymal Stem Cells; Pericytes; Stromal Cells
PubMed: 32387900
DOI: 10.1016/j.coi.2020.03.009 -
Journal of Orthopaedic Research :... Jun 2019Mesenchymal progenitor cells reside in all assayed vascularized tissues, and are broadly conceptualized to participate in homeostasis/renewal and repair. The application... (Review)
Review
Mesenchymal progenitor cells reside in all assayed vascularized tissues, and are broadly conceptualized to participate in homeostasis/renewal and repair. The application of mesenchymal progenitor cells has been studied for diverse orthopaedic conditions related to skeletal degeneration, regeneration, and tissue fabrication. One common niche for mesenchymal progenitors is the perivascular space, and in both mouse and human tissues, perivascular progenitor cells have been isolated and characterized. Of these "perivascular stem cells" or PSC, pericytes are the most commonly studied cells. Multiple studies have demonstrated the regenerative properties of PSC when applied to bone, including direct osteochondral differentiation, paracrine-induced osteogenesis and vasculogenesis, and immunomodulatory functions. The confluence of these effects have resulted in efficacious bone regeneration across several preclinical models. Yet, key topics of research in perivascular progenitors highlight our lack of knowledge regarding these cell populations. These ongoing areas of study include cellular diversity within the perivascular niche, tissue-specific properties of PSC, and factors that influence PSC-mediated regenerative potential. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1221-1228, 2019.
Topics: Animals; Bone Development; Bone Regeneration; Humans; Mesenchymal Stem Cells; Organ Specificity; Pericytes; Tissue Engineering
PubMed: 30908717
DOI: 10.1002/jor.24284 -
Angiogenesis Nov 2018Glioblastoma is the most common malignant brain cancer in adults, with poor prognosis. The blood-brain barrier limits the arrival of several promising anti-glioblastoma... (Review)
Review
Glioblastoma is the most common malignant brain cancer in adults, with poor prognosis. The blood-brain barrier limits the arrival of several promising anti-glioblastoma drugs, and restricts the design of efficient therapies. Recently, by using state-of-the-art technologies, including thymidine kinase targeting system in combination with glioblastoma xenograft mouse models, it was revealed that targeting glioblastoma-derived pericytes improves chemotherapy efficiency. Strikingly, ibrutinib treatment enhances chemotherapeutic effectiveness, by targeting pericytes, improving blood-brain barrier permeability, and prolonging survival. This study identifies glioblastoma-derived pericyte as a novel target in the brain tumor microenvironment during carcinogenesis. Here, we summarize and evaluate recent advances in the understanding of pericyte's role in the glioblastoma microenvironment.
Topics: Adenine; Animals; Blood-Brain Barrier; Brain Neoplasms; Drug Delivery Systems; Glioblastoma; Mice; Pericytes; Piperidines; Pyrazoles; Pyrimidines; Tumor Microenvironment; Xenograft Model Antitumor Assays
PubMed: 29761249
DOI: 10.1007/s10456-018-9621-x -
Journal of Cellular and Molecular... Dec 2012Mesenchymal stem/stromal cells (MSC) are currently the best candidate therapeutic cells for regenerative medicine related to osteoarticular, muscular, vascular and... (Review)
Review
Mesenchymal stem/stromal cells (MSC) are currently the best candidate therapeutic cells for regenerative medicine related to osteoarticular, muscular, vascular and inflammatory diseases, although these cells remain heterogeneous and necessitate a better biological characterization. We and others recently described that MSC originate from two types of perivascular cells, namely pericytes and adventitial cells and contain the in situ counterpart of MSC in developing and adult human organs, which can be prospectively purified using well defined cell surface markers. Pericytes encircle endothelial cells of capillaries and microvessels and express the adhesion molecule CD146 and the PDGFRβ, but lack endothelial and haematopoietic markers such as CD34, CD31, vWF (von Willebrand factor), the ligand for Ulex europaeus 1 (UEA1) and CD45 respectively. The proteoglycan NG2 is a pericyte marker exclusively associated with the arterial system. Besides its expression in smooth muscle cells, smooth muscle actin (αSMA) is also detected in subsets of pericytes. Adventitial cells surround the largest vessels and, opposite to pericytes, are not closely associated to endothelial cells. Adventitial cells express CD34 and lack αSMA and all endothelial and haematopoietic cell markers, as for pericytes. Altogether, pericytes and adventitial perivascular cells express in situ and in culture markers of MSC and display capacities to differentiate towards osteogenic, adipogenic and chondrogenic cell lineages. Importantly, adventitial cells can differentiate into pericyte-like cells under inductive conditions in vitro. Altogether, using purified perivascular cells instead of MSC may bring higher benefits to regenerative medicine, including the possibility, for the first time, to use these cells uncultured.
Topics: Adipose Tissue; Adventitia; Antigens; Biomarkers; CD146 Antigen; Cell Differentiation; Cell Lineage; Cell Transplantation; Cells, Cultured; Humans; Membrane Proteins; Mesenchymal Stem Cells; Pericytes; Proteoglycans; Receptor, Platelet-Derived Growth Factor beta; Regenerative Medicine
PubMed: 22882758
DOI: 10.1111/j.1582-4934.2012.01617.x -
Biomedicine & Pharmacotherapy =... Dec 2022Pericytes are mural vascular cells covering microvascular capillaries, where they contribute to the formation, maturation, maintenance, stabilisation and remodelling of... (Review)
Review
Pericytes are mural vascular cells covering microvascular capillaries, where they contribute to the formation, maturation, maintenance, stabilisation and remodelling of vasculature. They actively interact and communicate with other cells to maintain the capillary structural integrity, vascular permeability and blood flow. Pericytes are crucial participants in the physiological and pathological processes of cardiovascular disease. In this review, we summarise recent data regarding pericyte metabolism, trans-differentiation, angiogenesis and immunomodulation in connection with different cardiovascular pathologies. Further, we discuss an application of pericytes as a new cell therapy approach to treat coronary artery disease, congenital heart disease, atherosclerotic plaques calcification and calcific valvular heart disease in different in vivo animal models and in vitro studies. Also, we discuss different methods and pharmacological therapies for CVDs treatment with pericyte-mediated effects. Finally, we present a comprehensive overview of the role of pericytes in CVDs and as a pharmacological target for different novel drugs and techniques and highlight the potential application of pericytes to treat CVDs.
Topics: Animals; Pericytes; Cardiovascular Diseases; Capillaries; Neovascularization, Pathologic; Cell Differentiation
PubMed: 36411618
DOI: 10.1016/j.biopha.2022.113928 -
American Journal of Hematology Aug 2010Despite promising results in preclinical and clinical studies, the therapeutic efficacy of antiangiogenic therapies has been restricted by a narrow focus on inhibiting... (Review)
Review
Despite promising results in preclinical and clinical studies, the therapeutic efficacy of antiangiogenic therapies has been restricted by a narrow focus on inhibiting the growth of endothelial cells. Other cell types in the tumor stroma are also critical to the progression of cancer, including mural cells. Mural cells are vascular support cells that range in phenotype from pericytes to vascular smooth muscle cells. Although the role of pericytes and pericyte-like cells in the pathophysiology of cancer is still unclear, evidence indicates that aberrations in pericyte-endothelial cell signaling networks could contribute to tumor angiogenesis and metastasis. The purpose of this review is to evaluate critically recent evidence on the role of pericytes in tumor biology and discuss potential therapeutic targets for anticancer intervention.
Topics: Angiogenesis Inhibitors; Angiogenic Proteins; Animals; Endothelial Cells; Extracellular Matrix Proteins; Humans; Mice; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms; Neovascularization, Pathologic; Pericytes; Stromal Cells
PubMed: 20540157
DOI: 10.1002/ajh.21745