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Mesenchymal stem cell expressed VEGF‐E protects pulmonary endothelial cells from cigarette smoke toxicity (1176.9)
Author(s) -
Zhai Bo,
Zhang Li,
Huang Chaoqun,
Varshney Rohan,
Sivasami Pulavendran,
Hinsdale Myron,
Liu Lin,
Lloyd Pamela
Publication year - 2014
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.28.1_supplement.1176.9
Subject(s) - vascular endothelial growth factor , mesenchymal stem cell , medicine , paracrine signalling , lung , immunology , copd , angiogenesis , pulmonary edema , vascular endothelial growth factor a , cancer research , pharmacology , andrology , pathology , vegf receptors , receptor
Chronic obstructive pulmonary disease (COPD) is a major public health problem worldwide and the fourth leading cause of mortality in the US. COPD patients have compromised lung microvascular endothelial cells (EC) and decreased lung capillarity. Vascular endothelial growth factor (VEGF), a critical survival factor for EC, is reduced in lungs of COPD patients. Mesenchymal stem cells (MSC) are adult stem cells which secrete paracrine cytoprotective factors, including VEGF‐A. However, VEGF‐A is active at both VEGFR‐1 and VEGFR‐2, and VEGFR‐1 is implicated in the pathogenesis of COPD. Thus, we hypothesized that selective VEGFR‐2 activation would better protect lung EC from cigarette smoke induced damage in vitro. VEGF‐E, a VEGFR‐2 selective viral isoform, was expressed using a lentiviral vector in MSC isolated from bone marrow of C57BL/6 mice. Conditioned medium from wtMSC and VEGFE‐MSC was collected and concentrated 10‐fold. Primary human lung microvascular EC (HLMVEC) were then exposed to cigarette smoke extract (CSE,10%) ± wtMSC or VEGFE‐MSC conditioned medium (CM). HLMVEC treated with VEGFE‐MSC CM showed increased viability (MTT assay; absorbance at 570nm 0.295±0.073) after 24 h of CSE exposure , compared to wtMSC CM treated CSE‐exposed HLMVEC (absorbance 0.085±0.031, p<0.001).We next will compare the effects of VEGF‐A and VEGF‐E on endothelial permeability using a fluorescent dextran assay to determine whether VEGF‐E is less likely than VEGF‐A to cause increased permeability in vitro and edema in vivo. Studies to further characterize the effects of VEGFE‐MSC CM on EC in vitro are underway. Future studies will examine the ability of VEGFE‐MSC to repair the injured lung in COPD. Grant Funding Source : Supported by Oklahoma Center for Adult Stem Cell Research