DigitalUM :: Browsing by Subject "Pericytes"

Browsing by Subject "Pericytes"

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Open Access
Arterial wall neovascularization induced by glycerol
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Díaz Flores, L.; Gutierrez, R.; Valladares, F.; Díaz, M.; Valera, H.; Díaz Flores Jr, L.; Madrid Cuevas, Juan Francisco
An int e nse a nd sig ni fica nt neo - vascul ari za tion, with numerous capillaries growing into th e med ia laye r o f th e rat femo ra l art e ry, was demonstrated when glycero l was administered into the interstitium be tween the femoral ve in and the femoral a rt e ry. Th e max imum mi c rovasc ul a ri za ti o n was obse rved at days 7 and 9 after glyce rol administration. Afterwards, invo lution of th e majo rit y of the new lyfo rmed microvessels in the art erial wall occurred. Other substances containing glyce rol in their molecul es, such as tri ace tyl-glyce rol and tri butyril-glyce rol, fa il ed to produce significant neovascul ari zation in the medi a laye r of the femora l art ery. Neova cul ariza tion of the art eri al wa ll was preceded by a co nside rab le dec rease in the number of the smooth muscle ce lls, whi ch ex perienced apoptosis and necrobiosis, disappearing in extense areas of the arteri al segment affected by glyce rol. Coinciding with neovascul ariza tion and mi crovascul ar in volu tion, repopul ation of the med ia laye r by smooth mu 'cle cells was observed.
Open Access
Autophagy in the immunosuppressive perivascular microenvironment of glioblastoma
(MDPI, 2019-12-31) Molina Gallego, María Luisa; Martínez Pérez, Salvador; García Bernal, David; Valdor Alonso, Rut; Bioquímica y Biología Molecular B e Inmunología
Glioblastoma (GB) has been shown to up-regulate autophagy with anti- or pro-oncogenic effects. Recently, our group has shown how GB cells aberrantly up-regulate chaperone-mediated autophagy (CMA) in pericytes of peritumoral areas to modulate their immune function through cell-cell interaction and in the tumor’s own benefit. Thus, to understand GB progression, the effect that GB cells could have on autophagy of immune cells that surround the tumor needs to be deeply explored. In this review, we summarize all the latest evidence of several molecular and cellular immunosuppressive mechanisms in the perivascular tumor microenvironment. This immunosuppression has been reported to facilitate GB progression and may be differently modulated by several types of autophagy as a critical point to be considered for therapeutic interventions.
Open Access
Chaperone-mediated autophagy ablation in pericytes reveals new glioblastoma prognostic markers and efficient treatment against tumor progression
(2022-03-18) Molina Gallego, María Luisa; Aparicio, Pedro; Moraleda, José M.; Martínez, Salvador; García Bernal, David; Rubio Pedraza, Gonzalo; Salinas Hidalgo, María Dolores; Valdor Alonso, Rut; Bioquímica y Biología Molecular B e Inmunología
Background: The lack of knowledge of the progression mechanisms of glioblastoma (GB), the most aggressive brain tumor, contributes to the absence of successful therapeutic strategies. Our team has recently demonstrated a crucial new role for chaperone-mediated autophagy (CMA) in pericytes (PC)-acquired immunosuppressive function, which prevents anti-tumor immune responses and facilitates GB progression. The possible impact that GB-induced CMA in PC has on other functions that might be useful for future GB prognosis/treatment, has not been explored yet. Thus, we proposed to analyze the contribution of CMA to other GB-induced changes in PC biology and determine if CMA ablation in PC is a key target mechanism for GB treatment. Methods: Studies of RNA-seq and secretome analysis were done in GB-conditioned PC with and without CMA (from knockout mice for LAMP-2A) and compared to control PC. Different therapeutic strategies in a GB mouse model were compared. Results: We found several gene expression pathways enriched in LAMP2A-KO PC and affected by GB-induced CMA in PC that correlate with our previous findings. Phagosome formation, cellular senescence, focal adhesion and the effector function to promote anti-tumor immune responses were the most affected pathways, revealing a transcriptomic profiling of specific target functions useful for future therapies. In addition, several molecules associated with tumor mechanisms and related to tumor immune responses such as gelsolin, periostin, osteopontin, lumican and vitamin D, were identified in the PC secretome dependent on GB-induced CMA. The CMA ablation in PC with GB cells showed an expected immunogenic phenotype able to phagocyte GB cells and a key strategy to develop future therapeutic strategies against GB tumor progression. A novel intravenous therapy using exofucosylated CMA-deficient PC was efficient to make PC reach the tumor niche and facilitate tumor elimination. Conclusion: Our results corroborate previous findings on the impaired immunogenic function of PC with GB-induced CMA, driving to other altered PC functions and the identifications of new target markers related to the tumor immune responses and useful for GB prognosis/therapy. Our work demonstrates CMA ablation in PC as a key target mechanism to develop a successful therapy against GB progression.
Open Access
Chaperone-Mediated Autophagy in Pericytes: A Key Target for the Development of New Treatments against Glioblastoma Progression
(MDPI, 2022-08-10) Salinas Hidalgo, María Dolores; Valdor Alonso, Rut; Bioquímica y Biología Molecular B e Inmunología
Open Access
Datos de investigación Proyecto Estudio de la Biología del Pericito Dependiente de Autofagia Mediada por Chaperonas Como Diana Clave para el Desarrrollo de Terapias en Glioblastoma (PID2023-149111OB-I00)
(2026-05-19) Salinas Hidalgo, María Dolores; Naranjo Sánchez, Elena; Valdor Alonso, Rut; Martínez González, Isabel María; Bioquímica y Biología Molecular B e Inmunología; Facultades de la UMU::Facultad de Medicina
Open Access
Defining adipose tissue-derived stem cells in tissue and in culture
(Murcia: F. Hernández, 2010) Lin, Ching-Shwun; Xin, Zhong-Cheng; Deng, Chun-Hua; Ning, Hongxiu; Lin, Guiting; Lue, Tom F.
Adipose tissue-derived stem cells (ADSC) are routinely isolated from the stromal vascular fraction (SVF) of homogenized adipose tissue. Similar to other types of mesenchymal stem cells (MSC), ADSC remain difficult to define due to the lack of definitive cellular markers. Still, many types of MSC, including ADSC, have been shown to reside in a perivascular location, and increasing evidence shows that both MSC and ADSC may in fact be vascular stem cells (VSC). Locally, these cells differentiate into smooth muscle and endothelial cells that are assembled into newly formed blood vessels during angiogenesis and neovasculogenesis. Additionally, MSC or ADSC can also differentiate into tissue cells such as adipocytes in the adipose tissue. Systematically, MSC or ADSC are recruited to injury sites where they participate in the repair/regeneration of the injured tissue. Due to the vasculature’s dynamic capacity for growth and multipotential nature for diversification, VSC in tissue are individually at various stages and on different paths of differentiation. Therefore, when isolated and put in culture, these cells are expected to be heterogeneous in marker expression, renewal capacity, and differentiation potential. Although this heterogeneity of VSC does impose difficulties and cause confusions in basic science studies, its impact on the development of VSC as a therapeutic cell source has not been as apparent, as many preclinical and clinical trials have reported favorable outcomes. With this understanding, ADSC are generally defined as CD34+CD31- although loss of CD34 expression in culture is well documented. In adipose tissue, CD34 is localized to the intima and adventitia of blood vessels but not the media where cells expressing alpha-smooth muscle actin (SMA) exist. By excluding the intima, which contains the CD34+CD31+ endothelial cells, and the media, which contains the CD34-CD31- smooth muscle cells, it leaves the adventitia as the only possible location for the CD34+ ADSC. In the capillary, CD34 and CD140b (a pericyte marker) are mutually exclusively expressed, thus suggesting that pericytes are not the CD34+ ADSC. Many other cellular markers for vascular cells, stem cells, and stem cell niche have also been investigated as possible ADSC markers. Particularly the best-known MSC marker STRO-1 has been found either expressed or not expressed in cultured ADSC. In the adipose tissue, STRO-1 appears to be expressed exclusively in the endothelium of certain but not all blood vessels, and thus not associated with the CD34+ ADSC. In conclusion, we believe that ADSC exist as CD34+CD31-CD104b-SMA- cells in the capillary and in the adventitia of larger vessels. In the capillary these cells coexist with pericytes and endothelial cells, both of which are possibly progenies of ADSC (or more precisely VSC). In the larger vessels, these ADSC or VSC exist as specialized fibroblasts (having stem cell properties) in the adventitia.
Open Access
Immunophenotypical analyses of myofibroblasts in rat excisional wound healing: possible transdifferentiation of blood vessel pericytes and perifollicular dermal sheath cells into myofibroblasts
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Juniantito, Vetnizah; Izawa, Takeshi; Yuasa, Takahiro; Ichikawa, Chisa; Kuwamura, Mitsuru; Yamate, Jyoji
Cutaneous fibrosis after wound is evoked by myofibroblasts capable of producing collagen; the derivation and features remain to be investigated. Immunophenotypical characteristics of myofibroblasts were analysed in excisional rat wound healing, of which samples were obtained on post-wounding (PW) days 1 to 26. Myofibroblasts were characterized for expressions of intermediate cytoskeletons such as vimentin, desmin, and α-smooth muscle actin (α-SMA). To pursue the progenitor, immunolabeling analyses were performed using stromal-/bone marrow-stem cell markers (Thy-1 and A3). Myofibroblasts reacting to vimentin and α-SMA were first seen on PW day 5, then peaked on PW day 9 in granulation tissues, and gradually decreased in remodeling tissues; these immunopositive cells reacted simultaneously to Thy-1. Desmin-reacting cells were limited to newly-formed blood vessels in wound bed. The single/double immunolabelings revealed that pericytes (identified by positive reaction to PDGFR-ß and negative reaction to endothelial markers) in newly-developing blood vessels reacted to vimentin, α-SMA, Thy-1 and A3, and occasionally to desmin, and that perifollicular dermal sheath cells in the wound periphery showed increased expressions for vimentin, Thy-1 and A3. There is considerable immunophenotypical similarity between myofibroblasts (expressing vimentin, α-SMA and Thy-1), pericytes (reacting to vimentin, α-SMA, Thy-1 and A3) in newly-developing blood vessels, and perifollicular dermal sheath cells (reacting to vimentin, Thy-1 and A3). Collectively, myofibroblasts in rat cutaneous fibrosis are characterized by vimentin, α-SMA and Thy-1 expressions, and the cells might be generated from the pericytes or perifollicular dermal sheath cells in the lineage of stroma-/bone marrow-stem cells
Open Access
Intussusceptive angiogenesis facilitated by microthrombosis has an important example in angiolipoma. An ultrastructural and immunohistochemical study
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Díaz Flores, Lucio; Gutiérrez, Ricardo; Pino García, Maria; González Gómez, Miriam; Díaz Flores Jr, Lucio; Carrasco, Jose Luis; Álvarez Argüelles, Hugo; Madrid Cuevas, Juan Francisco
The microvasculature of angiolipoma frequently presents thrombi. Our objectives are to assess whether intussusceptive angiogenesis (IA) participates in vasculature formation in non-infiltrating angiolipoma and, if so, to explore how thrombi are involved in the IA process. For this purpose, we studied angiolipoma specimens (n: 52), using immunohistochemistry, and confocal and electron microscopy. The results showed the presence of folds and pillars, hallmarks of IA, dividing the vessel lumen. Folds showed a cover formed by reoriented endothelial cells from the vessel wall, or from newly formed folds, and a core initially formed by thrombus fragments (clot components as transitional core), which was replaced by extracellular matrix and invaginating pericytes establishing numerous peg-andsocket junctions with endothelial cells (mature core). A condensed plasmatic electron-dense material surrounded and connected folds and pillars with each other and with the vascular wall, which suggests a clot role in fold/pillar arrangement. In conclusion, we contribute to IA participation in capillary network formation in angiolipoma and the immunohistochemical and ultrastructural events by which microthrombosis facilitates IA. Therefore, in addition to the histogenesis of angiolipoma, we provide an easily obtainable substrate for future studies on clot component action in IA, of clinical and therapeutic interest
Open Access
Kidney pericytes: A novel therapeutic target in interstitial fibrosis
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Smith, Stuart W.; Schrimpf, Claudia; Parekh, Dipen J.; Venkatachalam, Manjeri; Duffield, Jeremy S.
Chronic Kidney Disease affects approximately 8% of the population and contributes considerably to premature morbidity and mortality. Recently reported studies have highlighted an important role for resident microvascular pericytes in the pathogenesis of kidney fibrosis. Pericytes are emerging as the predominant source of the activated, matrix depositing, stromal cell population seen in progressive fibrosis. Further, pericyte activation leads to their detachment from the vasculature, triggers unstable microvasculature and leads to rarefaction. Strategies to modulate pericyte function in these processes are therefore therapeutically attractive. In this review we will first describe our current understanding of the structure and function of the pericyte and the role these cells play in angiogenesis and the pathogenesis of renal fibrosis. Novel therapeutic approaches targeting pericytes in murine models of renal disease will then be considered.
Open Access
Mesenchymal stem cells: from the perivascular environment to clinical applications
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Vezzani, Bianca; Pierantozzi, Enrico; Sorrentino, Vincenzo
Adult stem cells represent a fundamental biological system that has fascinated scientists over the last decades, and are currently the subject of a large number of studies aimed at better defining the properties of these cells, with a prominent focus on improving their application in regenerative medicine. One of the most used adult stem cells in clinical trials are mesenchymal stem cells (MSCs), which are multipotent cells able to differentiate into mature cells of mesodermal lineages. Following the initial studies on MSCs isolated from bone marrow, similar cells were also isolated from a variety of fetal and adult human tissues. Initially considered as identical and equipotent, MSCs from tissues other than bone marrow actually display differences in terms of their plastic abilities, which can be ascribed to the tissue of origin and/or to the procedures used for their isolation. Moreover, results from additional studies suggest that cultured MSCs represent the in vitro version of a subset of in vivo resident cells localized in the perivascular environment. In this review, we will focus our attention on MSCs from tissues other than bone marrow, their in vivo localization and their current applications in clinics.
Open Access
Microcirculation density and maturity in uterine and soft tissue leiomyosarcomas: an immunohistochemical study
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Caraffi, Stefano; Corradi, Domenico; Campanini, Nicoletta; Govoni, Paolo; Rocchi, Laura; Perris, Roberto; Mangieri, Domenica
The role of angiogenesis as a hallmark of tumor progression has been poorly explored in leiomyosarcoma, a rare but aggressive mesenchymal malignancy. We aimed to characterize microvessel distribution and morphology - including pericyte coverage - in a retrospective series of leyomiosarcomas of the soft tissues and the uterus. 41 whole-block tumor slides from formalin-fixed paraffin-embedded tissues were immunostained for endothelial-specific marker CD31 and microvessel density was quantified by assigning a grade to the frequency of CD31 positive microvessels. Vessel morphology and pericyte coverage were investigated by double-labeling for CD31 and either PDGFRβ, αSMA, desmin, CD90, or CD146. We found that microvessel density correlated with tumor grade in leiomyosarcoma of soft tissues, in analogy with what has been established in several types of carcinoma. This did not apply to uterine leiomyosarcoma, possibly due to the abundant myometrial vascularization. The evaluation of perivascular cell markers related to vessel stability revealed immature microvascular networks with aberrant pericyte coverage, irrespective of tumor origin or grade. Our observations substantiate the role of angiogenesis in the progression of soft tissue leiomyosarcoma. A multiple-marker approach to the assessment of pericyte coverage can identify different profiles of vessel immaturity correlated with tumor grade.
Open Access
Microvascular pericytes, a review of their morphological and functional characteristics
(Murcia : F. Hernández, 1991) Díaz-Flores, Lucio; Gutiérrez, Ricardo; Varela, Hilda; Rancel, N.; Valladares, Francisco
A hundred years after the first description, niany aspects of pericytes reniain to be examined. Mesenchymal in origin, pericytes form an incomplete envelopment around the endothelial cells and within the microvascular basement niernhrane of capillaries and postcapillary venules. Morphologically. they appear as long, slender, polymorphic cells. showing an elongated cell body, from which arise longitudinal and circumferential branches. Cell bodies and cytoplasmic processes of pericytes. as well as the endothelial cells, are enveloped by the same basal lamina. except for where they make direct contacts with each other. The pericytet endothelial cell contacts are peg and socket. adlicsion plaques and gap junctions. making up structural mechanisms for force transmission and a possible receptor system for cells, in which the pcricyte and endothelial cells I-espond to secondary signals generated in the other cells. Electron niicroscopic studies have revealed an elaborate network of cytoplasmic filaments. Pericytc intermediate filament proteins show species and tissue differences. expressing vimentin or vimentin and desmin. The pericytes also express protein typical of contractile cells, i.e. smooth muscle-specific isoforms of actin and myosin, cyclic GMP-protein kinase and tropomyosin. A gradual transition is observed between pericytes and smooth muscle cells in both terminal a-terioles and venules. Several general functions for the pericytes have been postulated: contractability: permeability regulator: integrity maintainer; endothelial cell growth modulator; and cell progenitor with considerable mesenchymal potential.
Open Access
Morphofunctional basis of the different types of angiogenesis and formation of postnatal angiogenesis-related secondary structures
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Díaz Flores, L.; Gutierrez, R.; García Suárez, M.P.; Sáez, F.J.; Gutiérrez, E.; Valladares, F.; Carrascosa, J.L.; Díaz Flores Jr, L.; Madrid Cuevas, Juan Francisco
We review the morpho-functional basis of the different types of angiogenesis and report our observations, including the formation of angiogenesisrelated secondary structures. First of all, we consider the following issues: a) conceptual differences between angiogenesis and vasculogenesis, b) incidence of angiogenesis in pre- and postnatal life, c) regions of vascular tree with angiogenic capacity, d) cells (endothelial cells, pericytes, CD34+ adventitial stromal cells of the microvasculature and inflammatory cells) and extracellular matrix components involved in angiogenesis, e) events associated with angiogenesis, f) different types of angiogenesis, including sprouting and intussusceptive angiogenesis, and other angiogenic or vascularization forms arising from endothelial precursor cells (postnatal vasculogenesis), vasculogenesis mimicry, vessel co-option and piecemeal angiogenesis. Subsequently, we consider the specific morphofunctional characteristics of each type of angiogenesis. In sprouting angiogenesis, we grouped the events in three phases: a) activation phase, which includes vasodilation and increased permeability, EC, pericyte and CD34+ adventitial stromal cell activation, and recruitment and activation of inflammatory cells, b)sprouting phase, encompassing EC migration (concept and characteristics of endothelial tip cells, tip cell selection, lateral inhibition, localized filopodia formation, basal lamina degradation and extracellular changes facilitating EC migration), EC proliferation (concept of endothelial stalk cells), pericyte mobilization, proliferation, recruitment and changes in CD34+ adventitial stromal cells and inflammatory cells, tubulogenesis, formation of a new basal lamina, and vascular anastomosis with capillary loop formation, and c) vascular remodelling and stabilization phase (concept of phalanx cells). Subsequently, the concept, incidence, events and mechanisms are considered in the other forms of angiogenesis. Finally, we contribute the formation of postnatal angiogenesis-related secondary structures: a) intravascular structures through piecemeal angiogenesis, including intravascular papillae in vessel tumours and pseudotumours (intravascular papillary endothelial hyperplasia, vascular transformation of the sinus in lymph nodes, papillary intralymphatic angioendothelioma or Dabska tumour, retiform hemangioendothelioma, hemangiosarcoma and lymphangiosarcoma), vascular septa in hemorrhoidal veins and intravascular projections in some tumours; b) arterial intimal thickening; c) intravascular tumours and pseudotumours (e.g. intravenous pyogenic granulomas and intravascular myopericytoma); d) vascular glomeruloid proliferations; and e) pseudopalisading necrosis in glioblastoma multiform.
Embargo
Pericytes, a cell type contributing to autoimmunity and immune tolerance
(Elsevier, 2023-06-16) Botía Sánchez, María; Molina, María Luisa; Aparicio, Pedro; Valdor Alonso, Rut; Bioquímica y Biología Molecular B e Inmunología
Pericytes have been, since their discovery, a very hard-to-define cell because of their unknown ontogeny and the lack of specific markers. As a consequence, several attempts to characterize both its molecular pattern and its metabolism have been carried out to describe the physiological role they play. Pericytes are located in the abluminal wall of small vessels and contribute to the maintenance of capillary tone and the regulation of oxygen flow to adjacent tissues, maintaining the homeostasis of the blood-brain barrier. Furthermore, they have been described as cells with immunological properties, being able to sense and secrete proinflammatory and antiinflammatory cytokines and to activate T cells, hence controlling the immune response. Interestingly, pericytes immune function might be modulated through molecular mechanisms such as chaperone-mediated autophagy, making them to convert from immunogenic to immunosuppressive cells contributing in autoimmunity and immune tolerance. The failure of the different pericytes functions which are implicated in the brain homeostasis is related with several pathologies associated to inflammation, including type 2 diabetes, multiple sclerosis, stroke, Alzheimer's disease, and cancer. In these scenarios, pericytes have always been proved as mediators of the pathology, which indicates that this barely-known type of cell might have a wide variety of unknown roles.
Open Access
Pericytes. Morphofunction, interactions and pathology in a quiescent and activated mesenchymal cell niche
(Murcia : F. Hernández, 2009) Díaz-Flores, Lucio; Gutiérrez, Ricardo; Varela, H.; Valladares, Francisco; Acosta, E.; Martín-Vasallo, P.; Díaz-Flores Jr., L.; Madrid Cuevas, Juan Francisco; Biología Celular
We review the morphofunctional characteristics of pericytes and report our observations. After a brief historical background, we consider the following aspects of pericytes: A) Origin in embryonic vasculogenesis (mesenchymal stem cells, neurocrest and other possible sources) and in embryonic and postnatal life angiogenesis (pre-existing pericytes, fibroblast/ myofibroblasts and circulating progenitor cells). B) Location in pericytic microvasculature and in the other blood vessels (including transitional cell forms and absence in lymphatic vessels), incidence (differences depending on species, topographical location, and type and stage of vessels) and distribution (specific polarities) in blood vessels. C) Morphology (cell body, and longitudinal and circumferential cytoplasmic processes), structure (nucleus, cytoplasmic organelles and distribution of microtubules, intermediate filaments and microfilaments) and surface (caveolae system). D) Basement membrane disposition, formation, components and functions. E) Contacts with endothelial cells (ECs) (peg and socket arrangements, adherent junctions and gap junctions) and with basal membrane (adhesion plaques). F) Molecular expression (pericyte marker identification). G) Functions, such as vessel stabilization, regulation of vascular tone and maintenance of local and tissue homeostasis (contractile capacity and vessel permeability regulation), matrix protein synthesis, macrophage-like properties, immunological defense, intervention in coagulation, participation in mechanisms that regulate the quiescent and angiogenic stages of blood vessels (including the behaviour of pericytes during sprouting angiogenesis and intussuceptive vascular growth, as well as pericyte interactions with endothelium and other cells, and with extracellular matrix) and plasticity, as progenitor cells with great mesenchymal potential, originating other pericytes, fibroblast/myofibroblasts, preadipocytes, chondroblasts, osteoblasts, odontoblasts, vascular smooth muscle and myointimal cells. This mesenchymal capacity is seen in a broad section on the perivascular mesenchymal cell niche hypothesis and in the concept of pericyte and EC “marriage and divorce”. H) Peculiar pericyte types, such as hepatic stellate cells (Ito cells), bone marrow reticular cells and mesangial cells. I) Involvement in pathological processes, such as repair through granulation tissue, pericyte-derived tumors, tumor angiogenesis and tumoral cell metastasis, diabetic microangiopathy, fibrosis, atherosclerosis and calcific vasculopathy, lymphedema distichiasis, chronic venous insufficiency, pulmonary hypertension, Alzheimer disease and multiple sclerosis. J) Clinical and therapeutic implications (de-stabilization of vessels or formation of a stable vasculature).
Open Access
Phenotypic changes and possible angiogenic roles of pericytes during wound healing in the mouse skin
(Editores F. Hernan dez y Juan F. Madrid. Murcia, Universidad de Murcia, Departamento de Biologia Celular e Histologia, 2011) Morikawa, Shunichi; Ezaki, Taichi
Pericytes (PCs) are attracting increasing attention as a crucial target for anti-angiogenic therapy. In this study, we sought to determine the functional significance of PCs during angiogenesis by using a skin wound healing model in which different angiogenic stages are identifiable. Angiogenesis was first observed on Day 3 after wounding and increased greatly on Day 5. On Day 5, the leading edge of the regenerating vessels (vascular advancing front; VAF) appeared to be composed of immature vessels, and was further divided into “tip” and “following” regions according to maturational differences. PCs distributed in regenerating vessels showed phenotypic differences according to different regions. PCs that expressed PDGFR-ß alone and lacked vascular basement membrane (BM) were predominant in the tip region of the VAF, while PCs that expressed both PDGFR-ß and NG2 with their BM coating were numerous in the following regions toward the rear of the VAF. Moreover, PCs in the VAF expressed VEGF-A and associated with most proliferating endothelial cells (ECs). VEGF-A expression of PCs and the proliferating ECs totally disappeared in the region toward the rear of the VAF. We conclude that PCs can differ in their phenotype according to the stage of angiogenesis during wound healing. They may promote angiogenesis at the initial stage but might in turn stabilize the newly formed vessels at the later stage.
Embargo
The effect of Glioblastoma on Pericytes
(2020-10-29) Molina Gallego, María Luisa; Valdor Alonso, Rut; Bioquímica y Biología Molecular B e Inmunología
Purpose of the Review: Intratumoral pericytes (PC) do not share the same tumor niche as peritumoral PC. Furthermore, glioblastoma multiforme (GB) cells do not seem to affect them equally. Therefore, for a better understanding of the effects of GB on PC, in this chapter, we will classify them according to whether they are intratumoral or peritumoral PC, focusing mainly on peritumoral effects, which seem to have better future prospects for finding effective therapies in GB cancer. Recent Findings: Recently, it has been shown that PC could be the main target of the tumor infiltration front and have a fundamental role in the proliferation, expansion, and survival of the tumor, as well as in the regulation of anti-tumor immune responses. Modulation of the immune function of PC through molecular mechanisms such as chaperone-mediated autophagy (CMA) seems to be essential to prevent an immunosuppressive microenviroment that facilitates tumor growth. Summary: GB is the most frequent and aggressive brain tumor. In the last years, PC have been gaining special attention due to their role in GB progression. GB cells infiltrate away from the tumor core more often and faster when they are associated with perivascular cells. However, to find targeted therapies against PC to promote their brain defense function and improve anti-tumor immune responses requires a better understanding of the heterogeneity, markers, and distribution of PC at origin.
Open Access
Ultrastructural characteristics of blood vessels in the infant and adult human cerebral cortex
(Murcia : F. Hernández, 1997) Zhang, H.F.; Ong, W.Y.; Leong, S.K.; Garey, L.J.
Blood vessels in frontal and temporal cerebral cortex of adults and two infants aged 5 months and 5 years were studied by electron microscopy. The cells outside the endothelium were classified on their ultrastructural characteristics. Fibroblasts had prominent rough endoplasmic reticulum and few mitochondria in the cytoplasm. They were different from pericytes, which contained a prominent Golgi apparatus but only a few, isolated profiles of rough endoplasmic reticulum. Smooth muscle cells were distinguished from fibroblasts and pericytes by the presence of filaments and caveolae. Perivascular cells were characterised by the presence of lysosomes and granules of different sizes and electron densities, and were present at al1 ages studied. Plasma cells had abundant rough endoplasmic reticulum in the cytoplasm, and were present only in the 5-month-old infant cortex. Cortical vessel diameter increased with age.

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