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

doi:10.1038/mt.2015.167

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 journal › Article › peer-review

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 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 language	English
Article number	12
Pages (from-to)	1854-1866
Number of pages	12
Journal	Molecular Therapy
Volume	23
Issue number	12
Early online date	6 Oct 2015
DOIs	https://doi.org/10.1038/mt.2015.167
Publication status	Published - Dec 2015

Access to Document

10.1038/mt.2015.167

Cardiac Nerve Growth Factor Overexpression Induces Bone Marrow–derived Progenitor Cells Mobilization and Homing to the Infarcted Heart
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/.
Final published version, 4.96 MBLicence: Creative Commons: Attribution-NonCommercial-ShareAlike (CC BY-NC-SA)

http://www.nature.com/doifinder/10.1038/mt.2015.167Licence: Creative Commons: Attribution Non-Commercial (CC-BY-NC)

Andrea Caporali
- A.Caporalied.acuk
- Deanery of Clinical Sciences - Senior Lecturer
- Centre for Cardiovascular Science
Person: Academic: Research Active

Cite this

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. (2015). Cardiac Nerve Growth Factor Overexpression Induces Bone Marrow–derived Progenitor Cells Mobilization and Homing to the Infarcted Heart. Molecular Therapy, 23(12), 1854-1866. Article 12. https://doi.org/10.1038/mt.2015.167

@article{e24b1dcd27194a05af08b68c1cee2d7a,

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

abstract = "Reparative response by bone marrow (BM)-derived progenitorcells (PCs) to ischemia is a multistep processthat comprises the detachment from the BM endostealniche through activation of osteoclasts and proteolyticenzymes (such as matrix metalloproteinases (MMPs)),mobilization to the circulation, and homing to theinjured tissue. We previously showed that intramyocardialnerve growth factor gene transfer (NGF-GT) promotescardiac repair following myocardial infarction(MI) in mice. Here, we investigate the impact of cardiacNGF-GT on postinfarction BM-derived PCs mobilizationand homing at different time points after adenovirusmediatedNGF-GT in mice. Immunohistochemistry andflow cytometry newly illustrate the temporal profile ofosteoclast and activation of MMP9, PCs expansion in theBM, and liberation/homing to the injured myocardium.NGF-GT amplified these responses and increased the BMlevels of active osteoclasts and MMP9, which were notobserved in MMP9-deficient mice. Taken together, ourresults suggest a novel role for NGF in BM-derived PCsmobilization/homing following MI.",

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

year = "2015",

month = dec,

doi = "10.1038/mt.2015.167",

language = "English",

volume = "23",

pages = "1854--1866",

journal = "Molecular Therapy",

issn = "1525-0016",

publisher = "Cell Press",

number = "12",

}

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, GD, Beltrami, AP & Emanueli, C 2015, 'Cardiac Nerve Growth Factor Overexpression Induces Bone Marrow–derived Progenitor Cells Mobilization and Homing to the Infarcted Heart', Molecular Therapy, vol. 23, no. 12, 12, pp. 1854-1866. https://doi.org/10.1038/mt.2015.167

TY - JOUR

T1 - Cardiac Nerve Growth Factor Overexpression Induces Bone Marrow–derived Progenitor Cells Mobilization and Homing to the Infarcted Heart

AU - Meloni, Marco

AU - Cesselli, Daniela

AU - Caporali, Andrea

AU - Mangialardi, Giuseppe

AU - Avolio, Elisa

AU - Reni, Carlotta

AU - Fortunato, Orazio

AU - Martini, Stefania

AU - Madeddu, Paolo

AU - Valgimigli, Marco

AU - Nikolaev, Evgeni

AU - Kaczmarek, Leszek

AU - Angelini, Gianni D

AU - Beltrami, Antonio P

AU - Emanueli, Costanza

PY - 2015/12

Y1 - 2015/12

N2 - Reparative response by bone marrow (BM)-derived progenitorcells (PCs) to ischemia is a multistep processthat comprises the detachment from the BM endostealniche through activation of osteoclasts and proteolyticenzymes (such as matrix metalloproteinases (MMPs)),mobilization to the circulation, and homing to theinjured tissue. We previously showed that intramyocardialnerve growth factor gene transfer (NGF-GT) promotescardiac repair following myocardial infarction(MI) in mice. Here, we investigate the impact of cardiacNGF-GT on postinfarction BM-derived PCs mobilizationand homing at different time points after adenovirusmediatedNGF-GT in mice. Immunohistochemistry andflow cytometry newly illustrate the temporal profile ofosteoclast and activation of MMP9, PCs expansion in theBM, and liberation/homing to the injured myocardium.NGF-GT amplified these responses and increased the BMlevels of active osteoclasts and MMP9, which were notobserved in MMP9-deficient mice. Taken together, ourresults suggest a novel role for NGF in BM-derived PCsmobilization/homing following MI.

AB - Reparative response by bone marrow (BM)-derived progenitorcells (PCs) to ischemia is a multistep processthat comprises the detachment from the BM endostealniche through activation of osteoclasts and proteolyticenzymes (such as matrix metalloproteinases (MMPs)),mobilization to the circulation, and homing to theinjured tissue. We previously showed that intramyocardialnerve growth factor gene transfer (NGF-GT) promotescardiac repair following myocardial infarction(MI) in mice. Here, we investigate the impact of cardiacNGF-GT on postinfarction BM-derived PCs mobilizationand homing at different time points after adenovirusmediatedNGF-GT in mice. Immunohistochemistry andflow cytometry newly illustrate the temporal profile ofosteoclast and activation of MMP9, PCs expansion in theBM, and liberation/homing to the injured myocardium.NGF-GT amplified these responses and increased the BMlevels of active osteoclasts and MMP9, which were notobserved in MMP9-deficient mice. Taken together, ourresults suggest a novel role for NGF in BM-derived PCsmobilization/homing following MI.

U2 - 10.1038/mt.2015.167

DO - 10.1038/mt.2015.167

M3 - Article

SN - 1525-0016

VL - 23

SP - 1854

EP - 1866

JO - Molecular Therapy

JF - Molecular Therapy

IS - 12

M1 - 12

ER -

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

Abstract

Access to Document

Fingerprint

Profiles

Andrea Caporali

Cite this