A three-cell type in vitro-model of BBB

Abstract 4372: Chronic myeloid leukemia (CML) exosomes promote angiogenesis in a Src-dependent fashion in vitro and in vivo

Abstract CML is an uncontrolled proliferation of bone marrow myeloid cells driven by the constitutively active fusion product tyrosine kinase BCR/ABL. Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is newly recognized as a factor in CML progression. Exosomes, released by a broad spectrum of cells, are microvesicles that play an important role in cell-to-cell communication both in physiological and pathological conditions. The role of exosomes released by CML cells in angiogenesis is emerging; however, little is known about the mechanisms involved in this process. We first isolated and characterized exosomes released by K562 CML cells and we demonstrated thei…

Exosomes released by k562 chronic myeloid leukemia cells promote endothelial cell tubular differentiation through uptake and cell-to-cell transfer

Exosomes, microvesicles of endocytic origin released by normal and tumor cells, play an important role in cell-to-cell ommunication. Angiogenesis has been shown to regulate progression of chronic myeloid leukemia (CML). The mechanism through which this happens has not been elucidated. We isolated and characterized exosomes from K562 CML cells and evaluated their effects on human umbilical endothelial cells (HUVECs). Fluorescent-labeled exosomes were nternalized by HUVECs during tubular differentiation on Matrigel. Exosome localization was perinuclear early in differentiation, moving peripherally in cells undergoing elongation and connection. Exosomes move within and between nanotubular stru…

Abstract 5135: Exosomes released by K562 chronic myeloid leukemia cells promote endothelial cell tubular differentiation through uptake and cell-to-cell transfer

Abstract We hypothesized that exosomes were a venue through which to transfer pro-angiogenic stimuli into and between endothelial cells during endothelial cell tubular differentiation. Exosomes are microvesicles of endocytic origin released by most normal and tumor cells that play an important role in cell-to-cell communication. Angiogenesis is recognized to be a factor in progression of chronic myeloid leukemia (CML). However, the mechanism through which this happens has not been elucidated. We first optimized and characterized secretion of exosomes from CML K562 cells, showing expected selective enrichment of exosomal markers CD63, CD81 and Tsg101 in exosomes compared to the K562 whole ce…

SHEDDING OF EXTRACELLULAR VESICLES FROM BRAIN CELLS

ASTROCYTES SHED EXTRACELLULAR VESICLES THAT CONTAIN FIBROBLAST GROWTH FACTOR-2 AND VASCULAR ENDOTHELIAL GROWTH FACTOR.

An important component of the pathogenic process of multiple sclerosis (MS) is the blood-brain barrier (BBB) damage. We recently set an in vitro model of BBB, based on a three-cell-type co-culture system, in which rat neurons and astrocytes synergistically induce brain capillary endothelial cells to form a monolayer with permeability properties resembling those of the physiological BBB. Herein we report that the serum from patients with secondary progressive multiple sclerosis (SPMS) has a damaging effect on isolated neurons. This finding suggests that neuronal damaging in MS could be a primary event and not only secondary to myelin damage, as generally assumed. SPMS serum affects the perme…

NOVEL ROUTES OF CELL TO CELL COMUNICATIONS AMONG BRAIN CELLS

Novel routes of cell to cell communications among brain cells

EXTRACELLULAR FACTORS INVOLVED IN THE INDUCTION OF BLOOD BRAIN BARRIER (BBB)

CARATTERIZZAZIONE DI NUOVI MARCATORI MOLECOLARI NELLA SCLEROSI MULTIPLA: UN APPROCCIO PROTEOMICO

AN IN VITRO MODEL OF BLOOD BRAIN BARRIER (BBB).

NEURONS PRODUCE FGF-2 AND VEGF SECRETE THEM AT LEST IN PART BY SHEDDING EXTRACELLULAR VESCICLES

Abstract We previously found that neurons are able to affect the ability of brain capillary endothelial cells to form in vitro a monolayer with properties resembling the blood-brain barrier. We then looked, by immunofluorescence and western analysis, for factors, produced by neurons, with the potential to influence growth and differentiation of endothelial cells. In the present paper, we report that neurons produce both vascular endothelial growth factor and fibroblast growth factor 2, two well-known angiogenic factors. More interestingly, we gained evidence that both factors are released by neurons, at least in part, by shedding of extracellular vesicles, that contain β1 integrin, a membra…

EXOSOMES RELEASED BY K562 CHRONIC MYELOID LEUKEMIA CELLS PROMOTE ENDOTHELIAL CELL TUBULAR DIFFERENTIATION THROUGH UPTAKE AND CELL-TO-CELL TRANSFER