Abstract
Pericytes are branched cells located in the wall of capillary blood vessels that are found throughout the body, embedded within the microvascular basement membrane and wrapping endothelial cells, with which they establish a strong physical contact. Pericytes regulate angiogenesis, vessel stabilization, and contribute to the formation of both the blood-brain and blood-retina barriers by Angiopoietin-1/Tie-2, platelet derived growth factor (PDGF) and transforming growth factor (TGF) signaling pathways, regulating pericyte-endothelial cell communication. Human pericytes that have been cultured for a long period give rise to multilineage progenitor cells and exhibit mesenchymal stem cell (MSC) features. We focused our attention on the roles of pericytes in brain and ocular diseases. In particular, pericyte involvement in brain ischemia, brain tumors, diabetic retinopathy, and uveal melanoma is described. Several molecules, such as adenosine and nitric oxide, are responsible for pericyte shrinkage during ischemia-reperfusion. Anti-inflammatory molecules, such as IL-10, TGFβ, and MHC-II, which are increased in glioblastoma-activated pericytes, are responsible for tumor growth. As regards the eye, pericytes play a role not only in ocular vessel stabilization, but also as a stem cell niche that contributes to regenerative processes in diabetic retinopathy. Moreover, pericytes participate in melanoma cell extravasation and the genetic ablation of the PDGF receptor reduces the number of pericytes and aberrant tumor microvessel formation with important implications for therapy efficacy. Thanks to their MSC features, pericytes could be considered excellent candidates to promote nervous tissue repair and for regenerative medicine.
Highlights
Located on the abluminal surface of capillary blood vessels throughout the body, pericytes are specialized cells with a pivotal role in vascular homoeostasis [1]
Another signaling pathway involved in both pericyte and endothelial cell proliferation, differentiation and survival is mediated by the transforming growth factor-β (TGF-β)
It is well known that pericyte loss and BRB breakdown play a central role in the pathological development of age-related macular degeneration, uveitis, and diabetic retinopathy (DR) [122]
Summary
Located on the abluminal surface of capillary blood vessels throughout the body, pericytes are specialized cells with a pivotal role in vascular homoeostasis [1]. Pericytes were described for the first time by Rouget in 1879, and for this reason they were first named “Rouget cells” Because of their location on the outer surface of blood capillaries and their close interaction with the underlying endothelial cells (ECs), with which they share the basement membrane, in 1923 Zimmermann renamed them “pericytes” (peri: around; cyte: cell) [2]. Brain and retinal pericytes arise from the neuroectodermal neural crest, whereas other similar cells (the ones of the trunk of the body) arise from the mesoderm leaflet [3]. These cells have a prominent nucleus and a small cytoplasmic volume, and present distinct morphology in different organs. In the light of what has been mentioned above, this review analyzes the state of the art of the research on the use of pericytes in the treatment of brain and ocular diseases
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