-
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 -
International Journal of Cancer Aug 2016The conventional view of tumour vascularization is that tumours acquire their blood supply from neighbouring normal stroma. Additional methods of tumour vascularization... (Review)
Review
The conventional view of tumour vascularization is that tumours acquire their blood supply from neighbouring normal stroma. Additional methods of tumour vascularization such as intussusceptive angiogenesis, vasculogenic mimicry, vessel co-option and vasculogenesis have been demonstrated to occur. However, the origin of the endothelial cells and pericytes in the tumour vasculature is not fully understood. Their origin from malignant cells has been shown indirectly in lymphoma and neuroblastoma by immuno-FISH experiments. It is now evident that tumours arise from a small population of cells called cancer stem cells (CSCs) or tumour initiating cells. Recent data suggest that a proportion of tumour endothelial cells arise from cancer stem cells in glioblastoma. This was demonstrated both in vitro and in vivo. The analysis of chromosomal abnormalities in endothelial cells showed identical genetic changes to those identified in tumour cells. However, another report contradicted these results from the earlier studies in glioblastoma and had shown that CSCs give rise to pericytes and not endothelial cells. The main thrust of this review is the critical analysis of the conflicting data from different studies and the remaining questions in this field of research. The mechanism by which this phenomenon occurs is also discussed in detail. The transdifferentiation of CSCs to endothelial cells/pericytes has many implications in the progression and metastasis of the tumours and hence it would be a novel target for antiangiogenic therapy.
Topics: Animals; Biomarkers; Cell Communication; Cell Transdifferentiation; Cell Transformation, Neoplastic; Endothelial Cells; Humans; Neoplasms; Neoplastic Stem Cells; Neovascularization, Pathologic; Pericytes; Signal Transduction
PubMed: 26934471
DOI: 10.1002/ijc.30067 -
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 -
Transplantation Apr 2015Chronic rejection of transplanted organs remains the main obstacle in the long-term success of organ transplantation. Thus, there is a persistent quest for development... (Review)
Review
Chronic rejection of transplanted organs remains the main obstacle in the long-term success of organ transplantation. Thus, there is a persistent quest for development of antichronic rejection therapies and identification of novel molecular and cellular targets. One of the potential targets is the pericytes, the mural cells of microvessels, which regulate microvascular permeability, development, and maturation by controlling endothelial cell functions and regulating tissue fibrosis and inflammatory response. In this review, we discuss the potential of targeting pericytes in the development of microvasular dysfunction and the molecular pathways involved in regulation of pericyte activities for antichronic rejection intervention.
Topics: Angiogenic Proteins; Animals; Cell Communication; Cell Transdifferentiation; Chronic Disease; Endothelial Cells; Fibrosis; Graft Rejection; Humans; Inflammation Mediators; Microcirculation; Microvessels; Myocytes, Smooth Muscle; Organ Transplantation; Pericytes; Signal Transduction; Treatment Outcome
PubMed: 25793439
DOI: 10.1097/TP.0000000000000648 -
Cancer Research Jun 2018The premetastatic niche formed by primary tumor-derived molecules contributes to fixation of cancer metastasis. The design of efficient therapies is limited by the... (Review)
Review
The premetastatic niche formed by primary tumor-derived molecules contributes to fixation of cancer metastasis. The design of efficient therapies is limited by the current lack of knowledge about the details of cellular and molecular mechanisms involved in the premetastatic niche formation. Recently, the role of pericytes in the premetastatic niche formation and lung metastatic tropism was explored by using state-of-the-art techniques, including lineage-tracing and mice with pericyte-specific KLF4 deletion. Strikingly, genetic inactivation of KLF4 in pericytes inhibits pulmonary pericyte expansion and decreases metastasis in the lung. Here, we summarize and evaluate recent advances in the understanding of pericyte contribution to premetastatic niche formation. .
Topics: Animals; Humans; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Lung; Lung Neoplasms; Neoplasm Metastasis; Pericytes
PubMed: 29789421
DOI: 10.1158/0008-5472.CAN-17-3883 -
Postepy Higieny I Medycyny... Mar 2017Pericytes, which are multi-potential stem cells, co-create the walls of the microvessels: capillaries, terminal arterioles and postcapillary venules. These cells are... (Review)
Review
Pericytes, which are multi-potential stem cells, co-create the walls of the microvessels: capillaries, terminal arterioles and postcapillary venules. These cells are localized under the basement membrane, tightly encircling the endothelium. The most frequently mentioned molecular markers of pericytes include NG2 (neural-glial antigen 2), β-type platelet-derived growth factor receptor (PDGFRβ), smooth muscle α-actin (α-SMA), regulator of G protein signalling 5 (RGS5), the adhesion protein CD146 and nestin. Different functions in physiological processes are assigned to pericytes such as maintaining the integrity and senescence of endothelial cells, transregulation of vascular tone or the potential to differentiate into other cells. Probably they are also involved in pathological processes such as tissues fibrosis. In this review, we focus on the participation of pericytes in the process of blood vessel formation, the regeneration of skeletal muscle tissue and fibrosis. Strong evidence for pericytes' participation in endothelial homeostasis, as well as in pathological conditions such as fibrosis, reveals a broad potential for the therapeutic use of these cells. Targeted pharmacological modulation of pericytes, leading to blocking signalling pathways responsible for the differentiation of pericytes into myofibroblasts, seems to be a promising strategy for the treatment of fibrosis in the early stages.
Topics: Actins; Animals; Biomarkers; Cell Differentiation; Endothelial Cells; Humans; Mesenchymal Stem Cells; Pericytes; Regeneration; Stem Cells
PubMed: 28345526
DOI: 10.5604/01.3001.0010.3803 -
Stem Cells and Development Apr 2013Mesenchymal stem cells (MSCs) exist in most adult tissues and have been located near or within blood vessels. Although "perivascular" has been commonly used to describe... (Review)
Review
Mesenchymal stem cells (MSCs) exist in most adult tissues and have been located near or within blood vessels. Although "perivascular" has been commonly used to describe such locations, increasing evidence points at the vessel wall as the exact location. Thus, "vascular stem cells (VSCs)" is recommended as a more accurate term for MSCs. Furthermore, 2 cell populations, namely pericytes and adventitial progenitor cells (APCs), are the likely VSCs. The pericyte evidence relies on the so-called pericyte-specific markers, but none of these markers is pericyte specific. In addition, pericytes appear to be too functionally diverse and sophisticated to have a large differentiation capacity. On the other hand, APCs are more naïve functionally and, therefore, more akin to being VSCs. In vitro, these cells spontaneously differentiate into pericytes, and can be induced to differentiate into vascular cells (endothelial and smooth muscle cells) and mesenchymal cells (e.g., bone, cartilage, and fat). In vivo, indirect evidence also points to their ability to differentiate into mesenchymal cells of their native tissue (e.g., fat). Moreover, they possess a large paracrine capacity and, therefore, can help maintain tissue homeostasis by encouraging the replication and differentiation of mesenchymal cells locally. These proposed in vivo functions are areas of interest for future research on VSCs.
Topics: Antigens, CD34; Biomarkers; Cell Differentiation; Cell Lineage; Endothelium, Vascular; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Pericytes
PubMed: 23330734
DOI: 10.1089/scd.2012.0504 -
Journal of Cerebral Blood Flow and... Jul 2020Pericytes, the mural cells surrounding microcirculation, are gaining increasing attention for their roles in health and disease of the central nervous system (CNS). As... (Review)
Review
Pericytes, the mural cells surrounding microcirculation, are gaining increasing attention for their roles in health and disease of the central nervous system (CNS). As an essential part of the neurovascular unit (NVU), pericytes are actively engaged in interactions with neighboring cells and work in synergy with them to maintain homeostasis of the CNS, such as maintaining the blood-brain barrier (BBB), regulating cerebral blood flow (CBF) and the glymphatic system as well as mediating immune responses. However, the dysfunction of pericytes may contribute to the progression of various pathologies. In this review, we discuss: (1) origin of pericytes and different pericyte markers; (2) interactions of pericytes with endothelial cells (ECs), astrocytes, microglia, oligodendrocytes, and neurons; (3) physiological roles of pericytes in the CNS; (4) effects of pericytes in different CNS diseases; (5) relationship of pericytes with extracellular vesicles (EVs) and microRNAs (miRs); (6) recent advances in pericytes studies and future perspective.
Topics: Animals; Central Nervous System Diseases; Homeostasis; Humans; Pericytes
PubMed: 32208803
DOI: 10.1177/0271678X20911331 -
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 -
The International Journal of... 2011Pericytes are branched cells embedded within the basement membrane of capillaries and post-capillary venules. They provide an incomplete investment to endothelial cells,... (Review)
Review
Pericytes are branched cells embedded within the basement membrane of capillaries and post-capillary venules. They provide an incomplete investment to endothelial cells, thus reinforcing vascular structure and regulating microvascular blood flow. Pericytes exert an important role on endothelial cell proliferation, migration and stabilization. Endothelial cells, in turn, stimulate expansion and activation of the pericyte precursor cell population. The balance between the number of endothelial cells and pericytes is highly controlled by a series of signaling pathway mechanisms operating in an autocrine and/or paracrine manner. In this review, we will first examine the molecular aspects of the pericyte activating factors secreted by endothelial cells, such as platelet derived growth factor B (PDGF-B), vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β) and angiopoietins (Angs), as well as signaling pathways involving Notch and ephrins. We will then consider the complex and multivarious contribution of pericytes to the different aspects of angiogenesis with particular emphasis on the potential role of these cells as targets in tumor therapy.
Topics: Cell Differentiation; Humans; Neovascularization, Physiologic; Pericytes; Protein Binding; Signal Transduction
PubMed: 21710434
DOI: 10.1387/ijdb.103167dr