Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model.
BACKGROUND
Bone marrow-derived stem cells are under investigation as a treatment for ischemic heart disease. Mesenchymal stem cells (MSCs) have been used preferentially in the acute ischemia model; data in the chronic ischemia model are lacking.


RESULTS
Twelve dogs underwent ameroid constrictor placement. Thirty days later, they received intramyocardial injections of either MSCs (100x10(6) MSCs/10 mL saline) (n=6) or saline only (10 mL) (controls) (n=6). All were euthanized at 60 days. Resting and stress 2D echocardiography was performed at 30 and 60 days after ameroid placement. White blood cell count (WBC), C-reactive protein (CRP), creatine kinase MB (CK-MB), and troponin I levels were measured. Histopathological and immunohistochemical analyses were performed. Mean left ventricular ejection fraction was similar in both groups at baseline but significantly higher in treated dogs at 60 days. WBC and CRP levels were similar over time in both groups. CK-MB and troponin I increased from baseline to 48 hours, eventually returning to baseline. There was a trend toward reduced fibrosis and greater vascular density in the treated group. MSCs colocalized with endothelial and smooth muscle cells but not with myocytes.


CONCLUSIONS
In a canine chronic ischemia model, MSCs differentiated into smooth muscle cells and endothelial cells, resulting in increased vascularity and improved cardiac function.
Silva
Guilherme V
GV
Texas Heart Institute at St Luke's Episcopal Hospital, Houston, Tex 77030, USA.
Litovsky
Silvio
S
Assad
Joao A R
JA
Sousa
Andre L S
AL
Martin
Bradley J
BJ
Vela
Deborah
D
Coulter
Stephanie C
SC
Lin
Jing
J
Ober
Judy
J
Vaughn
William K
WK
Branco
Rodrigo V C
RV
Oliveira
Edie M
EM
He
Rumin
R
Geng
Yong-Jian
YJ
Willerson
James T
JT
Perin
Emerson C
EC
D000818:Animals; D002097:C-Reactive Protein / Q000032:analysis; D002454:Cell Differentiation; D019070:Cell Lineage; D003331:Coronary Vessels / Q000166:cytology / Q000473:pathology; D003402:Creatine Kinase / Q000097:blood; D052279:Creatine Kinase, MB Form; D004285:Dogs; D042783:Endothelial Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000166:cytology*; D005260:Female; D005355:Fibrosis; D015552:Injections, Intralesional; D007527:Isoenzymes / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D017202:Myocardial Ischemia / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D018919:Neovascularization, Physiologic; D009928:Organ Specificity; D010641:Phenotype; D013318:Stroke Volume; D019210:Troponin I / Q000097:blood; D014463:Ultrasonography
D007527:Isoenzymes; D019210:Troponin I; D002097:C-Reactive Protein; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form