Transepicardial autologous bone marrow-derived mononuclear cell therapy in a porcine model of chronically infarcted myocardium.
OBJECTIVE
Cell therapy is becoming a viable strategy to improve revascularization and myocardial function after myocardial injury. We evaluated the effect of bone marrow-derived mononuclear cell (BMMNC) transplantation on collateral vessel development and myocardial function in a porcine model of chronically infarcted heart.


METHODS
Myocardial infarction was produced in 13 domestic swine. At 4 weeks, animals were randomized to receive transepicardial injections of autologous BMMNCs (approximately 24x10(6) cells, n=8) or phosphate buffered saline (PBS; control, n=5) into infarcted and border regions. Collateral growth, angiogenesis, and infarct size were assessed by angiography, immunohistochemistry, and histomorphometry.


RESULTS
Regional contractility was assessed by transepicardial echocardiography at baseline and 4 weeks following treatment. Angiography revealed a trend toward increased collateral growth in the BMMNC group. Wall motion score index (myocardial function) was similar in both groups at baseline (1.63+/-0.16 vs. 1.25+/-0.25, P=.21) and at 4 weeks (1.83+/-0.22 vs. 1.63+/-0.38, P=.62). alpha-Actin-positive smooth muscle cells (SMCs) and Factor VIII positive endothelial cells were significantly greater in the BMMNC-injected animals (314.8+/-37.4/0.1 vs. 167.1+/-11.9/0.1 mm(2) in controls, P=.02, and 363.3+/-28.2 cells/0.1 mm(2) vs. 254.4+/-28.1 cells/0.1 mm(2) in controls, P=.03, respectively). The number of blood vessels >50 mum in diameter was significantly increased in the BMMNC group (317.9+/-54.9 vs. 149.1+/-6.1, P<.05). The size of the infarct area was smaller in the BMMNC-transplanted group than in the controls (P=.015).


CONCLUSIONS
BMMNC transplantation appears to improve angiogenesis and reduce infarct size yet results in no improvement in left ventricular function in a chronically infarcted heart.
Waksman
Ron
R
Washington Hospital Center, Suite 4B-1, 110 Irving Street, NW, Washington, DC 20010, USA. ron.waksman@medstar.net
Fournadjiev
Jana
J
Baffour
Richard
R
Pakala
Rajbabu
R
Hellinga
David
D
Leborgne
Laurent
L
Yazdi
Hamid
H
Cheneau
Edouard
E
Wolfram
Roswitha
R
Seabron
Rufus
R
Horton
Kenneth
K
Kolodgie
Frank
F
Virmani
Renu
R
Rivera
Elias
E
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D002908:Chronic Disease; D003097:Collateral Circulation; D017023:Coronary Angiography; D004195:Disease Models, Animal; D004452:Echocardiography; D007124:Immunoenzyme Techniques; D009000:Monocytes / Q000637:transplantation*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000502:physiology; D011897:Random Allocation; D013552:Swine; D014182:Transplantation, Autologous