Intravenous infusion of bone marrow mesenchymal stem cells improves myocardial function in a rat model of myocardial ischemia.
OBJECTIVE
We investigated the effects of three different sites for delivery of bone marrow mesenchymal stem cells (MSCs) in a rat model of myocardial ischemia.


METHODS
Prospective, randomized, controlled study.


METHODS
University affiliated research institute.


METHODS
Male Sprague-Dawley rats.


METHODS
A thoracotomy was performed under general anesthesia. Myocardial ischemia was induced by ligation of the left anterior descending coronary artery. One month later, animals were randomized to receive 5 x 10(6) MSCs labeled with PKH26 in phosphate buffer solution or phosphate buffer solution alone as a placebo by injection into right femoral vein, directly into the left ventricular (LV) cavity, or into the ischemic zone in the anterior ventricular free wall.


RESULTS
Echocardiographically measured myocardial function, including ejection fraction and fractional shortening, was quantitated 2 wks and 4 wks after administering MSCs or phosphate buffer solution. Hemodynamics, including cardiac index, LV dP/dt40, LV negative dP/dt, and LV diastolic pressure were measured 4 wks after administering MSCs or phosphate buffer solution. MSCs were counted in 5-microm sections obtained with cryostat from each harvested heart. Significant improvements in ejection fraction, fractional shortening, cardiac index, LV dP/dt40, LV negative dP/dt, and LV diastolic pressure followed injection of MSCs, regardless of the site of injection. However, the number of MSCs counted in the heart sections was significantly greater after direct myocardial injection.


CONCLUSIONS
Independently of the site of injection and regardless of the different concentration of bone marrow mesenchymal stem cells identified in the myocardium, myocardial function was comparably improved in all groups of animals treated with MSCs.
Wang
Tong
T
Weil Institute of Critical Care Medicine, Rancho Mirage, CA, USA. drsheart@aol.com
Tang
Wanchun
W
Sun
Shijie
S
Ristagno
Giuseppe
G
Huang
Zitong
Z
Weil
Max Harry
MH
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D007262:Infusions, Intravenous; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley