Systemic delivery of adult stem cells improves cardiac function in spontaneously hypertensive rats.
1. Heart regeneration after myocardial infarction (MI) can occur after cell therapy, but the mechanisms, cell types and delivery methods responsible for this improvement are still under investigation. In the present study, we evaluated the impact of systemic delivery of bone marrow cells (BMC) and cultivated mesenchymal stem cells (MSC) on cardiac morphology, function and mortality in spontaneously hypertensive rats (SHR) submitted to coronary occlusion. 2. Female syngeneic adult SHR, submitted or not (control group; C) to MI, were treated with intravenous injection of MSC (MI + MSC) or BMC (MI + BM) from male rats and evaluated after 1, 15 and 30 days by echocardiography. Systolic blood pressure (SBP), functional capacity, histology, mortality rate and polymerase chain reaction for the Y chromosome were also analysed. 3. Myocardial infarction induced a decrease in SBP and BMC, but not MSC, prevented this decrease. An improvement in functional capacity and ejection fraction (38 +/- 4, 39 +/- 3 and 58 +/- 2% for MI, MI + MSC and MI + BM, respectively; P < 0.05), as well as a reduction of the left ventricle infarcted area, were observed in rats from the MI + BM group compared with the other three groups. Treated animals had a significantly reduced lesion tissue score. The mortality rate in the C, MI + BM, MI + MSC and MI groups was 0, 0, 16.7 and 44.4%, respectively (P < 0.05 for the MI + MSC and MI groups compared with the C and MI + BM groups). 4. The results of the present study suggest that systemic administration of BMC can improve left ventricular function, functional capacity and, consequently, reduce mortality in an animal model of MI associated with hypertension. We speculate that the cells transiently home to the myocardium, releasing paracrine factors that recruit host cells to repair the lesion.
Braga
Luisa M G de Macedo
LM
Department of Genetics, Federal University of Rio Grande do Sul, and State Foundation of Production and Research in Health of Rio Grande do Sul, Porto Alegre, Brazil.
Rosa
Kaleizu
K
Rodrigues
Bruno
B
Malfitano
Christiane
C
Camassola
Melissa
M
Chagastelles
Pedro
P
Lacchini
Silvia
S
Fiorino
Patricia
P
De Angelis
Kátia
K
Schaan
Beatriz D'Agord
BD
Irigoyen
Maria C
MC
Nardi
Nance Beyer
NB
D053687:Adult Stem Cells / Q000378:metabolism / Q000637:transplantation*; D000818:Animals; D001794:Blood Pressure; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000601:surgery; D004195:Disease Models, Animal; D005260:Female; D006973:Hypertension / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery*; D008026:Ligation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D012038:Regeneration; D013318:Stroke Volume; D013997:Time Factors; D014463:Ultrasonography; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling; D014998:Y Chromosome / Q000378:metabolism