Cardiac atrial appendage stem cells engraft and differentiate into cardiomyocytes in vivo: A new tool for cardiac repair after MI.
BACKGROUND
This study assessed whether autologous transplantation of cardiac atrial appendage stem cells (CASCs) preserves cardiac function after myocardial infarction (MI) in a minipig model.


RESULTS
CASCs were isolated from right atrial appendages of Göttingen minipigs based on high aldehyde dehydrogenase activity and expanded. MI was induced by a 2h snare ligation of the left anterior descending coronary artery. Upon reperfusion, CASCs were intramyocardially injected under NOGA guidance (MI-CASC, n=10). Non-transplanted pigs (MI, n=8) received sham treatment. 3D electromechanical mapping (EMM) and cardiac MRI were performed to assess left ventricular (LV) function. MI pigs developed LV dilatation at 2 months (2M), while in the MI-CASC group volumes remained stable. Global LV ejection fraction decreased by 16 ± 8% in MI animals vs 3 ± 10% in MI-CASC animals and regional wall thickening in border areas was better preserved in the MI-CASC group. EMM showed decreased viability and wall motion in the LV for both groups POST-MI, whereas at 2M these parameters only improved in the MI-CASC. Substantial cell retention was accompanied by cardiomyogenic differentiation in 98±1% of the transplanted CASCs, which functionally integrated. Second harmonic generation microscopy confirmed the formation of mature sarcomeres in transplanted CASCs. Absence of cardiac arrhythmias indicated the safety of CASC transplantation.


CONCLUSIONS
CASCs preserve cardiac function by extensive engraftment and cardiomyogenic differentiation. Our data indicate the enormous potential of CASCs in myocardial repair.
Laboratory of Experimental Hematology, Jessa Hospital, Hasselt, Belgium; Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.
Yanick
Y
Fanton
Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium; Department of Cardiothoracic Surgery, Jessa Hospital, Hasselt, Belgium.
Boris
B
Robic
Laboratory of Experimental Hematology, Jessa Hospital, Hasselt, Belgium; Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.
Jean-Luc
JL
Rummens
Laboratory of Experimental Hematology, Jessa Hospital, Hasselt, Belgium.
Annick
A
Daniëls
Laboratory of Experimental Hematology, Jessa Hospital, Hasselt, Belgium; Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.
Severina
S
Windmolders
Laboratory of Experimental Hematology, Jessa Hospital, Hasselt, Belgium; Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.
Leen
L
Willems
Department of Cardiac Anesthesia, Jessa Hospital, Hasselt, Belgium.
Luc
L
Jamaer
Department of Cardiac Anesthesia, Jessa Hospital, Hasselt, Belgium.
Jasperina
J
Dubois
MRI Unit-Department of Radiology, Jessa Hospital, Hasselt, Belgium.
Eric
E
Bijnens
MRI Unit-Department of Radiology, Jessa Hospital, Hasselt, Belgium.
Nic
N
Heuts
Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium; Biomedical Research Institute, Hasselt University, Hasselt, Belgium.
Kristof
K
Notelaers
Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium; Biomedical Research Institute, Hasselt University, Hasselt, Belgium.
Rik
R
Paesen
Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium; Biomedical Research Institute, Hasselt University, Hasselt, Belgium.
Marcel
M
Ameloot
Department of Cardiothoracic Surgery, Jessa Hospital, Hasselt, Belgium.
Urbain
U
Mees
Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium; Biomedical Research Institute, Hasselt University, Hasselt, Belgium.
Virginie
V
Bito
Laboratory of Experimental Hematology, Jessa Hospital, Hasselt, Belgium; Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.
Jeroen
J
Declercq
Laboratory of Experimental Hematology, Jessa Hospital, Hasselt, Belgium; Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.
Karen
K
Hensen
Laboratory of Experimental Hematology, Jessa Hospital, Hasselt, Belgium; Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.
Remco
R
Koninckx
Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium; Department of Cardiothoracic Surgery, Jessa Hospital, Hasselt, Belgium. Electronic address: marc.hendrikx@jessazh.be.
Marc
M
Hendrikx
D000818:Animals; D020517:Atrial Appendage / Q000166:cytology / Q000502:physiology* / Q000637:transplantation*; D005260:Female; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000502:physiology; D013552:Swine; D013556:Swine, Miniature; D014182:Transplantation, Autologous
Cardiac stem cell; Differentiation; Magnetic resonance imaging; Mapping; Myocardial infarction