Noninvasive quantification and optimization of acute cell retention by in vivo positron emission tomography after intramyocardial cardiac-derived stem cell delivery.
OBJECTIVE
The aim of this study was to quantify acute myocardial retention of cardiac-derived stem cells (CDCs) and evaluate different delivery methods with positron emission tomography (PET).


BACKGROUND
Success of stem cell transplantation for cardiac regeneration is partially limited by low retention/engraftment of the delivered cells. A clinically applicable method for accurate quantification of cell retention would enable optimization of cell delivery.


METHODS
The CDCs were derived from syngeneic, male Wistar Kyoto (WK) rats labeled with [(18)F]-fluoro-deoxy-glucose ((18)FDG) and injected intramyocardially into the ischemic region of female WK rats after permanent left coronary artery ligation. The effects of fibrin glue (FG), bradycardia (adenosine), and cardiac arrest were examined. Imaging with (18)FDG PET was performed for quantification of cell retention. Quantitative polymerase chain reaction (PCR) for the male-specific SRY gene was performed to validate the PET results.


RESULTS
Myocardial retention of cells suspended in phosphate-buffered saline 1 h after delivery was 17.6 +/- 11.5% by PCR and 17.8 +/- 7.3% by PET. When CDCs were injected immediately after induction of cardiac arrest, retention was increased to 75.6 +/- 18.6%. Adenosine slowed the ventricular rate and doubled CDC retention (35.4 +/- 5.3%). A similar increase in CDC retention was observed after epicardial application of FG at the injection site (37.5 +/- 8.2%). The PCR revealed a significant increase in 3-week cell engraftment in the FG animals (22.1 +/- 18.6% and 5.3 +/- 3.1%, for FG and phosphate-buffered saline, respectively).


CONCLUSIONS
In vivo PET permits accurate measurement of CDC retention early after intramyocardial delivery. Sealing injection sites with FG or lowering ventricular rate by adenosine might be clinically translatable methods for improving stem cell engraftment in a beating heart.
Terrovitis
John
J
The Heart Institute, Cedars Sinai Medical Center, Los Angeles, California 90048, USA.
Lautamäki
Riikka
R
Bonios
Michael
M
Fox
James
J
Engles
James M
JM
Yu
Jianhua
J
Leppo
Michelle K
MK
Pomper
Martin G
MG
Wahl
Richard L
RL
Seidel
Jurgen
J
Tsui
Benjamin M
BM
Bengel
Frank M
FM
Abraham
M Roselle
MR
Marbán
Eduardo
E
D000818:Animals; D002470:Cell Survival; D003331:Coronary Vessels / Q000601:surgery; D005260:Female; D006321:Heart / Q000502:physiology*; D008026:Ligation; D008297:Male; D023421:Models, Animal; D017202:Myocardial Ischemia / Q000628:therapy*; D009206:Myocardium; D032383:Myocytes, Cardiac / Q000637:transplantation*; D049268:Positron-Emission Tomography; D051381:Rats; D011921:Rats, Inbred WKY; D012038:Regeneration; D033581:Stem Cell Transplantation / Q000379:methods*