Autologous bone marrow cell implantation attenuates left ventricular remodeling and improves heart function in porcine myocardial infarction: an echocardiographic, six-month angiographic, and molecular-cellular study.
BACKGROUND
We investigated the potential benefits and the underlying mechanisms of autologous bone marrow-derived mononuclear cell (BMDMNC) implantation in a porcine model of acute anterior wall myocardial infarction (AAWMI) by studying 6-month left ventricular (LV) function and LV remodeling.


METHODS
After being aspirated from the iliac crest and cultured for 1 week, BMDMNCs were implanted immediately after AAWMI induction through the left anterior descending artery ligation. Thirty male mini-pigs (16-18 kg) were equally divided into group 1 [AAWMI plus saline injection into infarct-ischemia area (IA)], group 2 (AAWMI plus 3.0 × 10⁷ BMDMNC transplantation into non-IA), group 3 (AAWMI plus 3.0 × 10⁷ BMDMNC transplantation into IA), group 4 (sham control plus 3.0 × 10⁷ BMDMNC transplantation into LV myocardium), and group 5 (normal control).


RESULTS
By day 90, echocardiography demonstrated an increased LV end-diastolic and end-systolic dimensions but reduced LV ejection fraction (LVEF) in groups 1 and 2 than in other groups (all p < 0.01). Six-month angiographic study showed a lower LVEF and wall motion score but a higher mitral regurgitation in groups 1 and 2 than in other groups (all p < 0.01). In IA and peri-infarct area, the number of small vessels and mRNA expressions of endothelial nitric oxide synthase, Bcl-2, interleukin (IL)-10, and peroxisome proliferator-activated receptor-γ coactivator-1α were lower, whereas the number of apoptotic nuclei, caspase-3, Bax, endothelin-1, IL-8, and matrix metalloproteinase was higher in groups 1 and 2 than in other groups (all p < 0.01).


CONCLUSIONS
Autologous BMDMNC transplantation into IA rather non-IA improves LV function and reduces LV remodeling via eliciting a broad-spectrum of molecular-cellular defensive mechanisms.
Leu
Steve
S
Department of Cardiology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC.
Sun
Cheuk-Kwan
CK
Sheu
Jiunn-Jye
JJ
Chang
Li-Teh
LT
Yuen
Chun-Man
CM
Yen
Chia-Hung
CH
Chiang
Chiang-Hua
CH
Ko
Sheung-Fat
SF
Pei
Sung-Nan
SN
Chua
Sarah
S
Youssef
Ali A
AA
Wu
Chiung-Jen
CJ
Yip
Hon-Kan
HK
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D002478:Cells, Cultured; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000502:physiology; D004195:Disease Models, Animal; D004452:Echocardiography; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000601:surgery*; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D014182:Transplantation, Autologous; D020257:Ventricular Remodeling / Q000502:physiology*