Cardiac Nerve Growth Factor Overexpression Induces Bone Marrow–derived Progenitor Cells Mobilization and Homing to the Infarcted Heart

Marco Meloni, Daniela Cesselli, Andrea Caporali, Giuseppe Mangialardi, Elisa Avolio, Carlotta Reni, Orazio Fortunato, Stefania Martini, Paolo Madeddu, Marco Valgimigli, Evgeni Nikolaev, Leszek Kaczmarek, Gianni D Angelini, Antonio P Beltrami, Costanza Emanueli

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Reparative response by bone marrow (BM)-derived progenitor
cells (PCs) to ischemia is a multistep process
that comprises the detachment from the BM endosteal
niche through activation of osteoclasts and proteolytic
enzymes (such as matrix metalloproteinases (MMPs)),
mobilization to the circulation, and homing to the
injured tissue. We previously showed that intramyocardial
nerve growth factor gene transfer (NGF-GT) promotes
cardiac repair following myocardial infarction
(MI) in mice. Here, we investigate the impact of cardiac
NGF-GT on postinfarction BM-derived PCs mobilization
and homing at different time points after adenovirusmediated
NGF-GT in mice. Immunohistochemistry and
flow cytometry newly illustrate the temporal profile of
osteoclast and activation of MMP9, PCs expansion in the
BM, and liberation/homing to the injured myocardium.
NGF-GT amplified these responses and increased the BM
levels of active osteoclasts and MMP9, which were not
observed in MMP9-deficient mice. Taken together, our
results suggest a novel role for NGF in BM-derived PCs
mobilization/homing following MI.
Original languageEnglish
Article number12
Pages (from-to)1854-1866
Number of pages12
JournalMolecular Therapy
Volume23
Issue number12
Early online date6 Oct 2015
DOIs
Publication statusPublished - Dec 2015

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