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Advances in Experimental Medicine and... 2019The structural components of the umbilical cord, including two arteries and one vein, the stromal region/Wharton's jelly, and amniotic epithelial membrane, are well... (Review)
Review
The structural components of the umbilical cord, including two arteries and one vein, the stromal region/Wharton's jelly, and amniotic epithelial membrane, are well described at various time points of gestation. Over the last two decades, evidence has emerged that multipotent cells sharing properties of mesenchymal stromal cell and pericytes/mural cells can be isolated from multiple regions of the umbilical cord, including the perivascular region of the umbilical cord arteries and vein, Wharton's jelly, and subamnion. These cells have increasingly gained interest for their potential use in regenerative and immunomodulatory medicine. Recent studies suggest that obstetrical complications including gestational diabetes mellitus and preeclampsia may alter the yield, properties, and potency of mesenchymal stromal cells isolated from the umbilical cord. The role that pericytes or pericyte-like cells play in the development of the human umbilical cord and associated pathologies, however, remains to be investigated.
Topics: Amnion; Cell Differentiation; Female; Humans; Mesenchymal Stem Cells; Pericytes; Pregnancy; Pregnancy Complications; Umbilical Cord; Wharton Jelly
PubMed: 30937871
DOI: 10.1007/978-3-030-11093-2_12 -
Inflammopharmacology Jun 2020Diabetic retinopathy (DR) is a frequent complication of diabetes mellitus, and a common cause of vision impairment and blindness in these patients, yet many aspects of... (Review)
Review
Diabetic retinopathy (DR) is a frequent complication of diabetes mellitus, and a common cause of vision impairment and blindness in these patients, yet many aspects of its pathogenesis remain unresolved. Furthermore, current treatments are not effective in all patients, are only indicated in advanced disease, and are associated with significant adverse effects. This review describes the microvascular features of DR, and how pericyte depletion and low-grade chronic inflammation contribute to the pathogenesis of this common ophthalmic disorder. Existing, novel and investigational pharmacological strategies aimed at modulating the inflammatory component of DR and ameliorating pericyte loss to potentially improve clinical outcomes for patients with diabetic retinopathy, are discussed.
Topics: Animals; Diabetic Retinopathy; Humans; Inflammation; Pericytes
PubMed: 31612299
DOI: 10.1007/s10787-019-00647-9 -
Microcirculation (New York, N.Y. : 1994) Nov 2019Vascular pericytes provide critical contributions to the formation and integrity of the blood vessel wall within the microcirculation. Pericytes maintain vascular... (Review)
Review
Vascular pericytes provide critical contributions to the formation and integrity of the blood vessel wall within the microcirculation. Pericytes maintain vascular stability and homeostasis by promoting endothelial cell junctions and depositing extracellular matrix (ECM) components within the vascular basement membrane, among other vital functions. As their importance in sustaining microvessel health within various tissues and organs continues to emerge, so does their role in a number of pathological conditions including cancer, diabetic retinopathy, and neurological disorders. Here, we review vascular pericyte contributions to the development and remodeling of the microcirculation, with a focus on the local microenvironment during these processes. We discuss observations of their earliest involvement in vascular development and essential cues for their recruitment to the remodeling endothelium. Pericyte involvement in the angiogenic sprouting context is also considered with specific attention to crosstalk with endothelial cells such as through signaling regulation and ECM deposition. We also address specific aspects of the collective cell migration and dynamic interactions between pericytes and endothelial cells during angiogenic sprouting. Lastly, we discuss pericyte contributions to mechanisms underlying the transition from active vessel remodeling to the maturation and quiescence phase of vascular development.
Topics: Animals; Basement Membrane; Cellular Microenvironment; Extracellular Matrix; Humans; Neovascularization, Physiologic; Pericytes
PubMed: 31066166
DOI: 10.1111/micc.12554 -
Hearing Research Oct 2023Pericytes are specialized mural cells surrounding endothelial cells in microvascular beds. They play a role in vascular development, blood flow regulation, maintenance... (Review)
Review
Pericytes are specialized mural cells surrounding endothelial cells in microvascular beds. They play a role in vascular development, blood flow regulation, maintenance of blood-tissue barrier integrity, and control of angiogenesis, tissue fibrosis, and wound healing. In recent decades, understanding of the critical role played by pericytes in retina, brain, lung, and kidney has seen significant progress. The cochlea contains a large population of pericytes. However, the role of cochlear pericytes in auditory pathophysiology is, by contrast, largely unknown. The present review discusses recent progress in identifying cochlear pericytes, mapping their distribution, and defining their role in regulating blood flow, controlling the blood-labyrinth barrier (BLB) and angiogenesis, and involvement in different types of hearing loss.
Topics: Humans; Pericytes; Endothelial Cells; Hearing Loss; Deafness; Cochlea
PubMed: 37651921
DOI: 10.1016/j.heares.2023.108877 -
Clinical Science (London, England :... Feb 2018The cerebrovasculature is a multicellular structure with varying rheological and permeability properties. The outer wall of the brain capillary endothelium is enclosed... (Review)
Review
The cerebrovasculature is a multicellular structure with varying rheological and permeability properties. The outer wall of the brain capillary endothelium is enclosed by pericytes and astrocyte end feet, anatomically assembled to guarantee barrier functions. We, here, focus on the pericyte modifications occurring in disease conditions, reviewing evidence supporting the interplay amongst pericytes, the endothelium, and glial cells in health and pathology. Deconstruction and reactivity of pericytes and glial cells around the capillary endothelium occur in response to traumatic brain injury, epilepsy, and neurodegenerative disorders, impacting vascular permeability and participating in neuroinflammation. As this represents a growing field of research, addressing the multicellular reorganization occurring at the outer wall of the blood-brain barrier (BBB) in response to an acute insult or a chronic disease could disclose novel disease mechanisms and therapeutic targets.
Topics: Animals; Biological Transport; Blood-Brain Barrier; Brain; Capillary Permeability; Humans; Neuroglia; Pericytes
PubMed: 29439117
DOI: 10.1042/CS20171634 -
International Journal of Molecular... Mar 2019Pericytes are multipotent cells of the vascular system with cytoplasmic extensions proximal to endothelial cells that occur along the abluminal surface of the... (Review)
Review
Pericytes are multipotent cells of the vascular system with cytoplasmic extensions proximal to endothelial cells that occur along the abluminal surface of the endothelium. The interactions between endothelial cells and pericytes are essential for proper microvascular formation, development, stabilization, and maintenance. Pericytes are essential for the regulation of paracellular flow between cells, transendothelial fluid transport, angiogenesis, and vascular immunosurveillance. They also influence the chemical composition of the surrounding microenvironment to protect endothelial cells from potential harm. Dysregulation or loss of pericyte function can result in microvascular instability and pathological consequences. Human pericytes have been shown to be targets for human cytomegalovirus (HCMV) infection and lytic replication that likely contribute to vascular inflammation. This review focuses on human vascular pericytes and their permissiveness for HCMV infection. It also discusses their implication in pathogenesis in the blood⁻brain barrier (BBB), the inner blood⁻retinal barrier (IBRB), the placenta⁻blood barrier, and the renal glomerulus as well as their potential role in subclinical vascular disease.
Topics: Animals; Cytomegalovirus; Cytomegalovirus Infections; Disease Susceptibility; Endothelium, Vascular; Female; Host-Pathogen Interactions; Humans; Mesangial Cells; Pericytes; Placenta; Pregnancy; Retina; Risk Assessment; Risk Factors
PubMed: 30909422
DOI: 10.3390/ijms20061456 -
Advances in Experimental Medicine and... 2018Studies of pericytes have been retarded by the lack of appropriate markers for identification of these perivascular mural cells. Use of antibodies against the NG2... (Review)
Review
Studies of pericytes have been retarded by the lack of appropriate markers for identification of these perivascular mural cells. Use of antibodies against the NG2 proteoglycan as a pericyte marker has greatly facilitated recent studies of pericytes, emphasizing the intimate spatial relationship between pericytes and endothelial cells, allowing more accurate quantification of pericyte/endothelial cell ratios in different vascular beds, and revealing the participation of pericytes throughout all stages of blood vessel formation. The functional importance of NG2 in pericyte biology has been established via NG2 knockdown (in vitro) and knockout (in vivo) strategies that reveal significant deficits in blood vessel formation when NG2 is absent from pericytes. NG2 influences pericyte proliferation and motility by acting as an auxiliary receptor that enhances signaling through integrins and receptor tyrosine kinase growth factor receptors. By acting in a trans orientation, NG2 also activates integrin signaling in closely apposed endothelial cells, leading to enhanced maturation and formation of endothelial cell junctions. NG2 null mice exhibit reduced growth of both mammary and brain tumors that can be traced to deficits in tumor vascularization. Use of Cre-Lox technology to produce pericyte-specific NG2 null mice has revealed specific deficits in tumor vessels that include decreased pericyte ensheathment of endothelial cells, diminished assembly of the vascular basement membrane, reduced vessel patency, and increased vessel leakiness. Interestingly, myeloid-specific NG2 null mice exhibit even larger deficits in tumor vascularization, leading to correspondingly slower tumor growth. Myeloid-specific NG2 null mice are deficient in their ability to recruit macrophages to tumors and other sites of inflammation. This absence of macrophages deprives pericytes of a signal that is crucial for their ability to interact with endothelial cells. The interplay between pericytes, endothelial cells, and macrophages promises to be an extremely fertile area of future study.
Topics: Animals; Antigens; Endothelial Cells; Inflammation; Macrophages; Mice; Neoplasms; Neovascularization, Pathologic; Pericytes; Proteoglycans
PubMed: 30523586
DOI: 10.1007/978-3-030-02601-1_2 -
Methods in Molecular Biology (Clifton,... 2021MicroRNAs (miRNAs) are expressed in all cell types, including pericytes, and play essential roles in vascular development, homeostasis, and disease. Manipulation of...
MicroRNAs (miRNAs) are expressed in all cell types, including pericytes, and play essential roles in vascular development, homeostasis, and disease. Manipulation of pericytes with miRNA mimics and inhibitors represents an essential tool to study the role of pericytes in vascular development and regeneration and to better understand the therapeutic potential of miRNA manipulation in pericytes. Here we describe methods for manipulating pericyte function by using miRNA mimics and inhibitors. We also describe methods to assess pericyte function (proliferation and migration) after manipulation with miRNAs and explain how miRNA gene targets can be identified and validated in pericytes after manipulation with miRNA.
Topics: Animals; Cloning, Molecular; Gene Expression Regulation; Humans; MicroRNAs; Pericytes; Transfection; Transformation, Genetic
PubMed: 33576975
DOI: 10.1007/978-1-0716-1056-5_10 -
Cells Mar 2021Pericytes, as mural cells covering microvascular capillaries, play an essential role in vascular remodeling and maintaining vascular functions and blood flow. Pericytes... (Review)
Review
Pericytes, as mural cells covering microvascular capillaries, play an essential role in vascular remodeling and maintaining vascular functions and blood flow. Pericytes are crucial participants in the physiological and pathological processes of cardiovascular disease. They actively interact with endothelial cells, vascular smooth muscle cells (VSMCs), fibroblasts, and other cells via the mechanisms involved in the secretome. The secretome of pericytes, along with diverse molecules including proinflammatory cytokines, angiogenic growth factors, and the extracellular matrix (ECM), has great impacts on the formation, stabilization, and remodeling of vasculature, as well as on regenerative processes. Emerging evidence also indicates that pericytes work as mesenchymal cells or progenitor cells in cardiovascular regeneration. Their capacity for differentiation also contributes to vascular remodeling in different ways. Previous studies primarily focused on the roles of pericytes in organs such as the brain, retina, lung, and kidney; very few studies have focused on pericytes in the heart. In this review, following a brief introduction of the origin and fundamental characteristics of pericytes, we focus on pericyte functions and mechanisms with respect to heart disease, ending with the promising use of cardiac pericytes in the treatment of ischemic heart failure.
Topics: Cell Differentiation; Endothelial Cells; Humans; Myocytes, Cardiac; Pericytes
PubMed: 33806335
DOI: 10.3390/cells10030548 -
Acta Neuropathologica Oct 2018Many central nervous system diseases currently lack effective treatment and are often associated with defects in microvascular function, including a failure to match... (Review)
Review
Many central nervous system diseases currently lack effective treatment and are often associated with defects in microvascular function, including a failure to match the energy supplied by the blood to the energy used on neuronal computation, or a breakdown of the blood-brain barrier. Pericytes, an under-studied cell type located on capillaries, are of crucial importance in regulating diverse microvascular functions, such as angiogenesis, the blood-brain barrier, capillary blood flow and the movement of immune cells into the brain. They also form part of the "glial" scar isolating damaged parts of the CNS, and may have stem cell-like properties. Recent studies have suggested that pericytes play a crucial role in neurological diseases, and are thus a therapeutic target in disorders as diverse as stroke, traumatic brain injury, migraine, epilepsy, spinal cord injury, diabetes, Huntington's disease, Alzheimer's disease, diabetes, multiple sclerosis, glioma, radiation necrosis and amyotrophic lateral sclerosis. Here we report recent advances in our understanding of pericyte biology and discuss how pericytes could be targeted to develop novel therapeutic approaches to neurological disorders, by increasing blood flow, preserving blood-brain barrier function, regulating immune cell entry to the CNS, and modulating formation of blood vessels in, and the glial scar around, damaged regions.
Topics: Animals; Blood-Brain Barrier; Capillaries; Humans; Nervous System Diseases; Pericytes
PubMed: 30097696
DOI: 10.1007/s00401-018-1893-0