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Mechanisms underlying hPMSC‐based protection on human brain endothelial cells
Author(s) -
Barzegar Mansoureh,
Minagar Alireza,
Wang Yuping,
Yun Jungmi W,
Boyer Christen,
Couraud PierreOlivier,
Alexander J.Steven
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb704
Subject(s) - blood–brain barrier , matrigel , mesenchymal stem cell , microbiology and biotechnology , stem cell , inflammation , medicine , endothelial stem cell , angiogenesis , tight junction , ischemia , basement membrane , cancer research , immunology , chemistry , biology , central nervous system , in vitro , biochemistry
Stroke remains among the leading causes of neurologically‐based morbidity and long‐term disability and results from thromboembolism (85% of strokes) or hemorrhage (15%). Several events lead to neuronal death in the stroke‐affected brain. Initially, production of local pro‐inflammatory mediators following brain ischemia/reperfusion promote stroke injury by decreasing blood‐brain barrier and by enhancing leukocyte binding and infiltration. Stem cell‐based therapies are a revolutionary treatment for several neurodegenerative diseases including stroke acting through neuronal cell trans‐differentiation but also provide acute protection properties by releasing substances which suppress inflammation, induce angiogenesis, and regulate vascular reactivity. We hypothesized that human placental‐derived mesenchymal stem cells (hPMSCs), a type of extraembryonic stem cell, might enhance acute protection against injury by releasing mediators which suppress the immune cell infiltration and maintain blood brain barrier. To investigate this, we examined the extent to which hPMSC conditioned media (CM) could mobilize junctional barrier‐creating proteins in human brain endothelial cells (hCMEC‐D3). We performed FITC‐Dextran permeability assays as well as junctional protein western blotting to evaluate the expression of junctional protein following treatment with hPMSC‐CM. We have also assessed the influence of hPMSC‐CM on contractility of human brain vascular smooth muscle cell (hBVSMC) using collagen gel contraction assay. Finally, we have used Matrigel Basement Membrane Matrix to follow up the formation of tubes from hCMEC‐D3 following treatment hPMSC‐CM. We found that passage four hPMSC‐CM improved the barrier function of hCMEC‐D3 and increased the expression of ZO‐1 and a‐Claudin‐1 proteins involved in tight junction. We also observed less contraction of hBVSMC treated with hPMSC‐CM. Moreover, hPMSC‐CM could accelerate the tube formation of hCMEC‐D3. We conclude that PMSC release stable factors which beneficially and acutely influence barrier structure and integrity. Therefore, PMSC may affect both acute as well as chronic phases of recovery in stroke.