-
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 -
Journal of Chemical Neuroanatomy Sep 2018The interest in investigating brain pericytes is growing due to their diverse influences on neuronal function. While numerous studies have investigated the particular... (Review)
Review
The interest in investigating brain pericytes is growing due to their diverse influences on neuronal function. While numerous studies have investigated the particular properties and functions of pericytes, complex insight into their functional histology is often lacking. In this work, we review and combine the current knowledge regarding brain pericyte function in normal physiology and its role in the pathogenesis of neurodegenerative diseases and tumorigenesis. Special attention is paid to the interaction between the components of the neurovascular unit. Finally, approaches used to detect brain pericytes and the methods for generating qualitative and quantitative data to assess pericyte changes are described.
Topics: Animals; Brain; Humans; Pericytes
PubMed: 29678665
DOI: 10.1016/j.jchemneu.2018.04.003 -
Thyroid : Official Journal of the... Jul 2023Anaplastic thyroid carcinoma (ATC) is a rapidly fatal cancer with a median survival of a few months. Enhanced therapeutic options for durable management of ATC will...
Anaplastic thyroid carcinoma (ATC) is a rapidly fatal cancer with a median survival of a few months. Enhanced therapeutic options for durable management of ATC will rely on an understanding of genetics and the role of the tumor microenvironment. The prognosis for patients with ATC has not improved despite more detailed scrutiny of underlying tumor genetics. Pericytes in the microenvironment play a key evasive role for thyroid carcinoma (TC) cells. Lenvatinib improves outcomes in patients with radioiodine-refractory well-differentiated TC. In addition to the unclear role of pericytes in ATC, the effect and mechanism of lenvatinib efficacy on ATC have not been sufficiently elucidated. We assessed pericyte enrichment in ATC. We determined the effect of lenvatinib on ATC cell growth cocultured with pericytes and in a xenograft mouse model from human -ATC-derived cells coimplanted with pericytes. ATC samples were significantly enriched in pericytes compared with normal thyroid samples. -ATC-derived cells were resistant to lenvatinib treatment shown by a lack of suppression of MAPK and Akt pathways. Moreover, lenvatinib increased CD47 protein (thrombospondin-1 [TSP-1] receptor) levels over time vs. vehicle. TSP-1 levels were downregulated upon lenvatinib at late vs. early time points. Critically, ATC cells, when cocultured with pericytes, showed increased sensitivity to this therapy and ultimately decreased number of cells. The coimplantation of ATC cells with pericytes increased ATC growth and did not downregulate TSP-1 in the microenvironment . Pericytes are enriched in ATC samples. Lenvatinib showed inhibitory effects on -ATC cells in the presence of pericytes. The presence of pericytes could be crucial for effective lenvatinib treatment in patients with ATC. Degree of pericyte abundance may be an attractive prognostic marker in assessing pharmacotherapeutic options. Effective durable management of ATC will rely on an understanding not only of genetics but also on the role of the tumor microenvironment.
Topics: Humans; Animals; Mice; Thyroid Carcinoma, Anaplastic; Pericytes; Thrombospondin 1; Tyrosine Kinase Inhibitors; Tumor Microenvironment; Proto-Oncogene Proteins B-raf; Iodine Radioisotopes; Thyroid Neoplasms; Protein Kinase Inhibitors; Disease Models, Animal
PubMed: 37171127
DOI: 10.1089/thy.2022.0597 -
Glia Aug 2023Cerebral blood flow (CBF) is important for the maintenance of brain function and its dysregulation has been implicated in Alzheimer's disease (AD). Microglia...
Cerebral blood flow (CBF) is important for the maintenance of brain function and its dysregulation has been implicated in Alzheimer's disease (AD). Microglia associations with capillaries suggest they may play a role in the regulation of CBF or the blood-brain-barrier (BBB). We explored the relationship between microglia and pericytes, a vessel-resident cell type that has a major role in the control of CBF and maintenance of the BBB, discovering a spatially distinct subset of microglia that closely associate with pericytes. We termed these pericyte-associated microglia (PEM). PEM are present throughout the brain and spinal cord in NG2DsRed × CX CR1 mice, and in the human frontal cortex. Using in vivo two-photon microscopy, we found microglia residing adjacent to pericytes at all levels of the capillary tree and found they can maintain their position for at least 28 days. PEM can associate with pericytes lacking astroglial endfeet coverage and capillary vessel width is increased beneath pericytes with or without an associated PEM, but capillary width decreases if a pericyte loses a PEM. Deletion of the microglia fractalkine receptor (CX CR1) did not disrupt the association between pericytes and PEM. Finally, we found the proportion of microglia that are PEM declines in the superior frontal gyrus in AD. In summary, we identify microglia that specifically associate with pericytes and find these are reduced in number in AD, which may be a novel mechanism contributing to vascular dysfunction in neurodegenerative diseases.
Topics: Mice; Humans; Animals; Pericytes; Mice, Transgenic; Microglia; Brain; Blood-Brain Barrier; Alzheimer Disease
PubMed: 36994950
DOI: 10.1002/glia.24371 -
Journal of Biomedical Science Mar 2018Pericytes are multipotent cells present in every vascularized tissue in the body. Despite the fact that they are well-known for more than a century, pericytes are still... (Review)
Review
BACKGROUND
Pericytes are multipotent cells present in every vascularized tissue in the body. Despite the fact that they are well-known for more than a century, pericytes are still representing cells with intriguing properties. This is mainly because of their heterogeneity in terms of definition, tissue distribution, origin, phenotype and multi-functional properties. The body of knowledge illustrates importance of pericytes in the regulation of homeostatic and healing processes in the body.
MAIN BODY
In this review, we summarized current knowledge regarding identification, isolation, ontogeny and functional characteristics of pericytes and described molecular mechanisms involved in the crosstalk between pericytes and endothelial or immune cells. We highlighted the role of pericytes in the pathogenesis of fibrosis, diabetes-related complications (retinopathy, nephropathy, neuropathy and erectile dysfunction), ischemic organ failure, pulmonary hypertension, Alzheimer disease, tumor growth and metastasis with the focus on their therapeutic potential in the regenerative medicine. The functions and capabilities of pericytes are impressive and, as yet, incompletely understood. Molecular mechanisms responsible for pericyte-mediated regulation of vascular stability, angiogenesis and blood flow are well described while their regenerative and immunomodulatory characteristics are still not completely revealed. Strong evidence for pericytes' participation in physiological, as well as in pathological conditions reveals a broad potential for their therapeutic use. Recently published results obtained in animal studies showed that transplantation of pericytes could positively influence the healing of bone, muscle and skin and could support revascularization. However, the differences in their phenotype and function as well as the lack of standardized procedure for their isolation and characterization limit their use in clinical trials.
CONCLUSION
Critical to further progress in clinical application of pericytes will be identification of tissue specific pericyte phenotype and function, validation and standardization of the procedure for their isolation that will enable establishment of precise clinical settings in which pericyte-based therapy will be efficiently applied.
Topics: Animals; Disease Progression; Humans; Pericytes; Regenerative Medicine
PubMed: 29519245
DOI: 10.1186/s12929-018-0423-7 -
Stem Cell Reports Oct 2023The formation of vascular structures is fundamental for in vitro tissue engineering. Vascularization can enable the nutrient supply within larger structures and...
The formation of vascular structures is fundamental for in vitro tissue engineering. Vascularization can enable the nutrient supply within larger structures and increase transplantation efficiency. We differentiated human induced pluripotent stem cells toward endothelial cells in 3D suspension culture. To investigate in vitro neovascularization and various 3D microenvironmental approaches, we designed a comprehensive single-cell transcriptomic study. Time-resolved single-cell transcriptomics of the endothelial and co-evolving mural cells gave insights into cell type development, stability, and plasticity. Transfer to a 3D hydrogel microenvironment induced neovascularization and facilitated tracing of migrating, coalescing, and tubulogenic endothelial cell states. During maturation, we monitored two pericyte subtypes evolving mural cells. Profiling cell-cell interactions between pericytes and endothelial cells revealed angiogenic signals during tubulogenesis. In silico discovered ligands were tested for their capability to attract endothelial cells. Our data, analyses, and results provide an in vitro roadmap to guide vascularization in future tissue engineering.
Topics: Humans; Endothelial Cells; Induced Pluripotent Stem Cells; Neovascularization, Physiologic; Coculture Techniques; Neovascularization, Pathologic; Pericytes
PubMed: 37714147
DOI: 10.1016/j.stemcr.2023.08.008 -
Advances in Experimental Medicine and... 20181. The human vocal fold is a vibrating tissue and vascular structures in organs which have the capacity to vibrate require a specific structure suitable for vibration.... (Review)
Review
1. The human vocal fold is a vibrating tissue and vascular structures in organs which have the capacity to vibrate require a specific structure suitable for vibration. 2. The structure of the blood vessels is unique at the vocal fold edge as a vibrating tissue, where only small vessels, including arterioles, venules, and capillaries, are present. The capillaries are distributed in the superficial layer of the lamina propria (Reinke's space). 3. The blood vessels enter the vocal fold edge from the anterior or posterior end of the membranous vocal fold and run essentially parallel to the vocal fold edge. 4. Many pericytes can be seen around the capillaries in the human vocal fold mucosa. The cell bodies of the pericytes attach to capillary endothelial cells, and the branching processes encircle the capillaries and attach to the capillary endothelial cells at the tips. The processes of pericytes are in close contact with endothelial cells, sharing a common basement membrane with them. The tips of the processes form intercellular tight junctions with endothelial cells. 5. The pericytes in the vocal fold mucosa appear to provide mechanical support and protection to the capillary walls, particularly during phonation. The pericytes also appear to regulate the diameter of the capillary during and after phonation. Pericytes are also thought to be critical cells in vascular biology and angiogenesis, especially in revascularization following vocal fold tissue injury. 6. At birth, pericytes have already encircled the capillaries in the newborn vocal fold mucosa. The pericytes appear ready to provide support and protection of the blood vessels just after birth. 7. Vascular structures and their permeability are related to the specific structures and specific diseases of the human vocal fold mucosa as a vibrating tissue.
Topics: Basement Membrane; Capillaries; Endothelial Cells; Humans; Infant, Newborn; Laryngeal Mucosa; Pericytes; Vocal Cords
PubMed: 30523591
DOI: 10.1007/978-3-030-02601-1_7 -
Pharmacological Research Jan 2018Clinical data and basic research indicate that the structural and functional alterations that characterize the evolution of cardiac disease towards heart failure may be,... (Review)
Review
Clinical data and basic research indicate that the structural and functional alterations that characterize the evolution of cardiac disease towards heart failure may be, at least in part, reversed. This paradigm shift is due to the accumulation of evidence indicating that, in peculiar settings, cardiomyocytes may be replenished. Moving from the consideration that cardiomyocytes are rapidly withdrawn from the cell cycle after birth, independent laboratories have tested the hypothesis that cardiac resident stem/progenitor cells resided in mammalian hearts and were important for myocardial repair. After almost two decades of intensive investigation, several (but partially overlapping) cardiac resident stem/progenitor cell populations have been identified. These primitive cells are characterized by mesenchymal features, unique properties that distinguish them from mesodermal progenitors residing in other tissues, and heterogeneous embryological origins (that include the neural crest and the epicardium). A further layer of complexity is related to the nature, in vivo localization and properties of mesodermal progenitors residing in adult tissues. Intriguingly, these latter, whose possible perivascular pericyte/mural cell origin has been shown, have been identified in human hearts too. However, their exact anatomical localization, pathophysiological role, and their relationship with cardiac stem/progenitor cells are emerging only recently. Therefore, aim of this review is to discuss the different origin, the distinct nature, and the complementary effect of cardiac stem cells and pericytes supporting regenerative strategies based on the combined use of both myogenic and angiogenic factors.
Topics: Animals; Heart Failure; Humans; Pericytes; Regeneration; Stem Cells
PubMed: 28578204
DOI: 10.1016/j.phrs.2017.05.023 -
Advances in Experimental Medicine and... 2018In the nineteenth century, a French researcher, Charles-Marie Benjamin Rouget, revealed a population of contractile cells associated with small blood vessels, which were... (Review)
Review
In the nineteenth century, a French researcher, Charles-Marie Benjamin Rouget, revealed a population of contractile cells associated with small blood vessels, which were initially named after him as the Rouget cells. In the twentieth century, a German scientist, Karl Wilhelm Zimmermann, called these cells "pericytes" due to their anatomical position located in a perivascular position. The word pericyte was derived from "peri" meaning "around" and "cyte" from the word "kytos" (cell), illustrating a cell encircling a blood vessel. Until now, pericytes are still identified partially based on their specific anatomical location and morphology. Pericytes are present in all vascularized tissues, surrounding blood vessel walls. They encircle endothelial cells and communicate with them along the length of the blood vessels by paracrine signaling and physical contacts. Previously, the accurate distinction of pericytes from other perivascular cells was difficult, as electron and light microscopy were the sole available techniques capable to image these cells, limiting the information acquired from those works. This resulted in the misleading assumption that pericytes are merely inert supporting cells, limited exclusively to the physiological function of vascular stability. In the last 10 years, the combination of fluorescent and confocal microscopy with genetic state-of-art techniques, such as fate lineage tracing, enabled remarkable progress in the discovery of multiple novel essential functions for pericytes in health and disease, before unexpected. Recently, the rapidly expanding understanding of the pathophysiological roles of pericytes drew the attention of several research groups. Now, we know, for instance, that pericytes may play immune functions: attract innate leukocytes to exit via sprouting blood vessels, regulate lymphocyte activation, and contribute to the clearance of toxic by-products, having direct phagocytic activity. Pericytes also may behave as stem cells, forming other cell populations, as well as regulate the behavior of other stem cells in their niches. Very little is known about the exact identity of pericyte ancestors within developing tissues, and there is evidence for multiple distinct developmental sources. Pericytes differ in their embryonic origins between tissues and also within the same organ. Importantly, pericytes from distinct tissues may differ in their distribution, morphology, expression of molecular markers, plasticity, and functions; and, even within the same organ, there are various pericyte subpopulations. This book describes the major contributions of pericytes to different organ biology in physiological and pathological conditions. Further insights into the biology of pericytes will have important implications for our understanding of organ development, homeostasis, and disease. This book's initial title was "Pericyte Biology: Development, Homeostasis, and Disease." However, due to the current great interest in this topic, we were able to assemble more chapters than would fit in one book, covering pericyte biology under distinct circumstances. Therefore, the book was subdivided into three volumes entitled: "Pericyte Biology: Novel Concepts," "Pericyte Biology in Different Organs," and "Pericyte Biology in Disease." Here, we present a selected collection of detailed chapters on what we know so far about pericytes. More than 30 chapters written by experts in the field summarize our present knowledge on pericyte biology. Here, we present a selected collection of detailed chapters on what we know so far about pericytes. More than 30 chapters written by experts in the field summarize our present knowledge on pericyte biology.
Topics: Homeostasis; Humans; Pericytes
PubMed: 30523585
DOI: 10.1007/978-3-030-02601-1_1 -
Journal of Cerebral Blood Flow and... Sep 2021Pericytes and endothelial cells share membranous interdigitations called "peg-and-socket" interactions that facilitate their adhesion and biochemical crosstalk during...
Pericytes and endothelial cells share membranous interdigitations called "peg-and-socket" interactions that facilitate their adhesion and biochemical crosstalk during vascular homeostasis. However, the morphology and distribution of these ultrastructures have remained elusive. Using a combination of 3D electron microscopy techniques, we examined peg-and-socket interactions in mouse brain capillaries. We found that pegs extending from pericytes to endothelial cells were morphologically diverse, exhibiting claw-like morphologies at the edge of the cell and bouton-shaped swellings away from the edge. Reciprocal endothelial pegs projecting into pericytes were less abundant and appeared as larger columnar protuberances. A large-scale 3D EM data set revealed enrichment of both pericyte and endothelial pegs around pericyte somata. The ratio of pericyte versus endothelial pegs was conserved among the pericytes examined, but total peg abundance was heterogeneous across cells. These data show considerable investment between pericytes and endothelial cells, and provide morphological evidence for pericyte somata as sites of enriched physical and biochemical interaction.
Topics: Animals; Brain; Disease Models, Animal; Endothelial Cells; Humans; Male; Mice; Microscopy, Electron, Scanning; Pericytes
PubMed: 33970018
DOI: 10.1177/0271678X211012836