Article (Scientific journals)
Pretreatment of adult bone marrow mesenchymal stem cells with cardiomyogenic growth factors and repair of the chronically infarcted myocardium
Bartunek, Joseph; Croissant, J. D.; Wijns, William et al.
2007In American Journal of Physiology - Heart and Circulatory Physiology, 292 (2), p. 1095-H1104
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Keywords :
cardiac repair; myogenesis; chronic myocardial infarction; heart failure
Abstract :
[en] The in vivo cardiac differentiation and functional effects of unmodified adult bone marrow mesenchymal stem cells (MSCs) after myocardial infarction (MI) is controversial. We postulated that ex vivo pretreatment of autologous MSCs using cardiomyogenic growth factors will lead to cardiomyogenic specification and will result in superior biological and functional effects on cardiac regeneration of chronically infarcted myocardium. We used a chronic dog MI model generated by ligation of the coronary artery (n = 30). Autologous dog bone marrow MSCs were isolated, culture expanded, and specified into a cardiac lineage by adding growth factors, including basic FGF, IGF-1, and bone morphogenetic protein-2. Dogs underwent cell injection > 8 wk after the infarction and were randomized into two groups. Group A dogs (n = 20) received MSCs specified with growth factors (147 +/- 96 x 10(6)), and group B (n = 10) received unmodified MSCs (168 +/- 24 x 10(6)). After the growth factor treatment, MSCs stained positive for the early muscle and cardiac markers desmin, antimyocyte enhancer factor-2, and Nkx2-5. In group A dogs, prespecified MSCs colocalized with troponin I and cardiac myosin. At 12 wk, group A dogs showed a significantly larger increase in regional wall thickening of the infarcted territory (from 22 +/- 8 to 32 +/- 6% in group A; P < 0.05 vs. baseline and group B, and from 19 +/- 7 to 21 +/- 7% in group B, respectively) and a decrease in the wall motion score index (from 1.60 +/- 0.05 to 1.35 +/- 0.03 in group A; P < 0.05 vs. baseline and group B, and from 1.58 +/- 0.07 vs. 1.56 +/- 0.08 in group B, respectively). The biological ex vivo cardiomyogenic specification of adult MSCs before their transplantation is feasible and appears to improve their in vivo cardiac differentiation as well as the functional recovery in a dog model of the chronically infarcted myocardium.
Disciplines :
Anatomy (cytology, histology, embryology...) & physiology
Cardiovascular & respiratory systems
Author, co-author :
Bartunek, Joseph
Croissant, J. D.
Wijns, William
Gofflot, Stéphanie ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
de Lavareille, Aurore
Vanderheyden, M.
Kaluzhny, Y.
Mazouz, N.
Willemsen, Philippe
Penicka, M.
Mathieu, M.
Homsy, C.
De Bruyne, B.
Mc Entee, Kathleen ;  Université de Liège - ULiège > Département clinique des animaux de compagnie et des équidés > Sémiologie et clinique médicale des petits animaux
Lee, I. W.
Heyndrickx, G. R.
More authors (6 more) Less
Language :
English
Title :
Pretreatment of adult bone marrow mesenchymal stem cells with cardiomyogenic growth factors and repair of the chronically infarcted myocardium
Publication date :
February 2007
Journal title :
American Journal of Physiology - Heart and Circulatory Physiology
ISSN :
0363-6135
eISSN :
1522-1539
Publisher :
Amer Physiological Soc, Bethesda, United States - Maryland
Volume :
292
Issue :
2
Pages :
H1095-H1104
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 05 January 2009

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