In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 119, No. suppl_1 ( 2016-07-22)
Abstract:
Neutrophils (PMNs) are a central mediator of oxidative stress and tissue necrosis following acute myocardial infarction and reperfusion (MI/R). Currently no effective treatment directed towards PMN mediated injury exists. Cell based therapies may represent a novel strategy to reduce the damaging effects of the early immune response following MI/R injury. In this study, we examine whether mesenchymal stem cells (MSCs) reduce markers of PMN mediated inflammation as a possible mechanism for cardio-protection. In vitro analysis of human PMNs was performed following inflammatory stimuli and co-culture with MSCs, MSC conditioned media (MSC-CM), or no treatment. H 2 O 2 production and super oxide (SO) release was measured by amplex red and hydrocyanine based assays respectively. There were significant reductions in H 2 O 2 (p 〈 0.0001, n=4) and SO (p 〈 0.001, n=4) when PMNs were co-cultured with MSCs and MSC-CM compared to PMNs cultured alone. In vivo studies were performed in rats following acute MI/R injury. Treatment subgroups included normal saline control or MSCs implanted onto the heart by means of hydrogel encapsulation. One day after MI/R, H 2 O 2 levels were significantly reduced in myocardial tissue when treated with MSCs compared to saline treated hearts (p 〈 0.05, n=5). Furthermore, infiltration of myocardium by CD45+ leukocytes was significantly reduced in animals treated with MSCs compared to saline treated controls as measured by flow cytometry (p 〈 0.05, n=4). The effect of MSCs on functional outcomes was confirmed by use of speckle-tracking echocardiography which demonstrated significant improvements in cardiac function in MSC treated animals compared to saline controls as early as days 7 and persisting to day 28 post injury (p 〈 0.017, n=5).This study demonstrates that MSCs modulate multiple pro-inflammatory functions of PMNs in vitro and is the first to demonstrate in vivo reductions in ROS production and leukocyte infiltration as a potential mechanism for cardio-protection following MI/R injury, allowing for earlier transition to regenerative processes. Future studies will determine whether PMN infiltration and markers of respiratory burst activity are reduced with MSC therapy.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/res.119.suppl_1.210
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2016
detail.hit.zdb_id:
1467838-X
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