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 journalArticle

Abstract

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 adenovirus-mediated 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.Molecular Therapy (2015); doi:10.1038/mt.2015.167.

Original languageEnglish
JournalMolecular Therapy
DOIs
Publication statusAccepted/In press - Sep 10 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Genetics
  • Drug Discovery
  • Pharmacology

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    Meloni, M., Cesselli, D., Caporali, A., Mangialardi, G., Avolio, E., Reni, C., Fortunato, O., Martini, S., Madeddu, P., Valgimigli, M., Nikolaev, E., Kaczmarek, L., Angelini, G. D., Beltrami, A. P., & Emanueli, C. (Accepted/In press). Cardiac Nerve Growth Factor Overexpression Induces Bone Marrow–derived Progenitor Cells Mobilization and Homing to the Infarcted Heart. Molecular Therapy. https://doi.org/10.1038/mt.2015.167