Adipose-derived cardiomyogenic cells: in vitro expansion and functional improvement in a mouse model of myocardial infarction.
OBJECTIVE
Cells derived from the stroma vascular fraction (SVF) of mouse adipose tissue can spontaneously give rise to rare, functional, cardiac-like cells in vitro. This study aimed to improve the production of adipose-derived cardiomyogenic cells (AD-CMG), to characterize them and to assess their cardiac fate and functional outcomes after their administration in a mouse model of acute myocardial infarction.


RESULTS
The culture process optimized to improve in vitro cardiac specification consisted of a primary culture of murine SVF cells in semi-solid methylcellulose medium, a selection of AD-CMG cell clusters, and a secondary culture and expansion in BHK21 medium. AD-CMG cells were CD29(+), CD31(-), CD34(-), CD44(+), CD45(-), CD81(+), CD90(-), CD117(-), and Flk-1(-) and expressed several cardiac contractile proteins. After 1, 2, and 4 weeks of their injection in mice having acute myocardial infarction, a strong presence of green fluorescent protein-positive cells was identified by immunohistochemistry as well as quantitative polymerase chain reaction. Echocardiography showed a significant reduction of remodelling and stability of left ventricle ejection fraction in the AD-CMG cell-treated group vs. controls. Vascular density analysis revealed that AD-CMG administration was also associated with stimulation of angiogenesis in peri-infarct areas.


CONCLUSIONS
Cardiomyogenic cells can be selected and expanded in large amounts from mouse adipose tissue. They can survive and differentiate in an acute myocardial infarction model, avoiding remodelling and impairment of cardiac function, and can promote neo-vascularization in the ischaemic heart.
Léobon
Bertrand
B
UMR 5241 CNRS UPS, CHU Rangueil, 31054 Toulouse, France.
Roncalli
Jérôme
J
Joffre
Carine
C
Mazo
Manuel
M
Boisson
Marie
M
Barreau
Corinne
C
Calise
Denis
D
Arnaud
Emmanuelle
E
André
Mireille
M
Pucéat
Michel
M
Pénicaud
Luc
L
Prosper
Felipe
F
Planat-Bénard
Valérie
V
Casteilla
Louis
L
D000273:Adipose Tissue / Q000166:cytology*; D053687:Adult Stem Cells / Q000166:cytology* / Q000502:physiology / Q000637:transplantation*; D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology / Q000637:transplantation*; D018919:Neovascularization, Physiologic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D033581:Stem Cell Transplantation; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology / Q000628:therapy; D020257:Ventricular Remodeling / Q000502:physiology
D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins