Direct injection of autologous mesenchymal stromal cells improves myocardial function.
Cell-based therapies have been employed with conflicting results. Whether direct injection of ex-vivo expanded autologous marrow stromal cells (MSCs) would improve the function of ischemic myocardium and enhance angiogenesis is not well defined. In a porcine model of chronic ischemia, MSCs were isolated and cultured for 4 weeks. Sixteen animals were random divided into two groups to receive either direct intramyocardial injection of autologous MSCs, or equal volumes and injections sites of saline. Cine MRI and epicardial echocardiography were performed just prior to the injections and again 6 weeks later at the time of sacrifice at which point tissue was also analyzed. Myocardial function as assessed by regional wall thickening (as measured by dobutamine stress echocardiograms) demonstrated a 40.9% improvement after cell treatment of the ischemic zone (p=0.016) whereas the saline treated animals only had a 3.7% change (p=0.82) compared to baseline. The left ventricular ejection fractions of MSC group showed 19.5% improvement from baseline 35.9+/-3.8% to 42.9+/-5.8% (p=0.049). Increased vascularity was found in the MSC group compared to controls (0.80+/-0.30 vs 0.50+/-0.19 capillary/myocyte ratio, p=0.018). Direct injection of autologous MSCs promotes angiogenesis and enhances the functional improvements following chronic myocardial ischemia. This suggests that the angiogenesis engendered by cell treatment may be physiologically meaningful by improving the contractility of ischemic myocardium.
Zhou
Yifu
Y
Cellular Biology Section, Cardiothoracic Surgery Research Program, NHLBI, National Institutes of Health, 10 Center Drive, MSC 1550, Building 10, Room 2N246, Bethesda, MD 20892-1550, USA. zhouyifu@mail.nih.gov
Wang
Suna
S
Yu
Zuxi
Z
Hoyt
Robert F
RF
Sachdev
Vandana
V
Vincent
Pamela
P
Arai
Andrew E
AE
Kwak
Minjung
M
Burkett
Sandra Sczerba
SS
Horvath
Keith A
KA
D000818:Animals; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D007267:Injections; D045164:Mesenchymal Stem Cell Transplantation; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology; D017154:Stromal Cells / Q000637:transplantation; D013552:Swine; D016276:Ventricular Function