Bone marrow-derived mesenchymal stem cell-loaded fibrin patches act as a reservoir of paracrine factors in chronic myocardial infarction.
The combination of mesenchymal stem cells and tissue-engineered fibrin patches improves the therapeutic efficacy of stem cells. In vivo cardiac magnetic resonance (4.7 Tesla) and ex vivo high-spatial resolution CMR were used to track the fate of human bone marrow-derived mesenchymal stem cell (BMSC) delivered on an epicardial scaffold and more specifically assess their potential intramyocardial migration. Fifty-seven nude rats underwent permanent coronary artery ligation. Two months later, those with a left ventricular ejection fraction ≤55% were randomly allocated to receive a patch loaded with human BMSC (BMSC-P, n = 10), a patch loaded with BMSCs labelled with iron oxide nanoparticles (BMSC*-P, n = 12), an acellular patch (A-P, n = 8) or to serve as sham-operated animals (SHAM, n = 7). BMSC secretion of cytokines and growth factors was evaluated with flow-cytometry. Cardiac functional parameters of cell-treated groups (BMSC*-P and BMSC-P) yielded significantly better outcomes than the SHAM group (p = 0.044 and p = 0.026, respectively, for ejection fraction). Angiogenesis was higher in the cell-patch than in control groups (e.g. BMSC*P vs. SHAM: p = 0.007). No BMSCs were identified into the myocardium on cardiac magnetic resonance or histological sections, although persisting BMSCs were identified on the epicardial surface 21 days post-transplantation in 10% of rats hearts (Lamin A/C and CD90 positive). Cytokine and growth factor profiling demonstrated an increase in their release by cells seeded in patches. The absence of stem cell migration into the myocardium and the persistence of stem cells on the epicardial surface suggest that fibrin patches are likely to act predominantly as reservoirs of paracrine factors. Copyright © 2017 John Wiley & Sons, Ltd.
Paris Cardiovascular Research Center, INSERM U970, Université Paris Descartes, Sorbonne Paris Cité, Paris.|Radiology Department, Assistance Publique - Hôpitaux de Paris, Hôpital Trousseau, Université Pierre et Marie Curie, Paris.
Eléonore
E
Blondiaux
Paris Cardiovascular Research Center, INSERM U970, Université Paris Descartes, Sorbonne Paris Cité, Paris.
Laetitia
L
Pidial
Paris Cardiovascular Research Center, INSERM U970, Université Paris Descartes, Sorbonne Paris Cité, Paris.|Plateforme d'imagerie du petit animal, Université Paris Descartes, Sorbonne Paris Cité, Paris.
Gwennhael
G
Autret
Paris Cardiovascular Research Center, INSERM U970, Université Paris Descartes, Sorbonne Paris Cité, Paris.
Gabriel
G
Rahmi
Paris Cardiovascular Research Center, INSERM U970, Université Paris Descartes, Sorbonne Paris Cité, Paris.|Plateforme d'imagerie du petit animal, Université Paris Descartes, Sorbonne Paris Cité, Paris.
Daniel
D
Balvay
Public Health Department, Hôpital Henri Mondor, Créteil, LIC EA4393, Assistance Publique - Hôpitaux de Paris, Université Paris Est, Créteil.
Etienne
E
Audureau
Laboratoire matières et systèmes complexes (MSC), UMR 7057 CNRS, Université Paris-Diderot, Paris.
Claire
C
Wilhelm
Paris Cardiovascular Research Center, INSERM U970, Université Paris Descartes, Sorbonne Paris Cité, Paris.
Coralie L
CL
Guerin
Department of Pathology, Hôpital Européen Georges Pompidou, Assistance Publique - Hôpitaux de Paris, Paris.
Patrick
P
Bruneval
Paris Cardiovascular Research Center, INSERM U970, Université Paris Descartes, Sorbonne Paris Cité, Paris.
Jean-Sébastien
JS
Silvestre
Paris Cardiovascular Research Center, INSERM U970, Université Paris Descartes, Sorbonne Paris Cité, Paris.|Department of Cardiovascular Surgery, Assistance Publique - Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris.
Philippe
P
Menasché
Paris Cardiovascular Research Center, INSERM U970, Université Paris Descartes, Sorbonne Paris Cité, Paris.
Olivier
O
Clément
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000494:pharmacology*; D005434:Flow Cytometry; D006334:Heart Function Tests; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D019899:Paracrine Communication; D010496:Pericardium / Q000378:metabolism; D011923:Rats, Nude
D016207:Cytokines; D005337:Fibrin
cell transplantation; heart failure; magnetic resonance imaging; stem cell; tissue engineering