Bone marrow cell therapy prevents infarct expansion and improves border zone remodeling after coronary occlusion in rats.
BACKGROUND
Since the cell therapy benefits for myocardial infarction are mainly related to infarct reduction by regenerating lost myocardium or increasing survival of tissues at risk, we evaluated the effects of bone marrow-derived mononuclear cells (MNC), implanted after the completion of necrosis, on infarct progression and cardiac remodeling.


METHODS
After 48 h of induction of myocardial infarction (MI), Lewis-inbred rats were injected with 6 × 10(6) cells (MI+MNC) or saline (MI). After six weeks, scar dimension, ventricular morphology and function were analyzed by echocardiography followed by histomorphology of the infarcted and border zones.


RESULTS
After therapy, the relative size of the infarct was smaller in MI+MNC (37 ± 1% of the left ventricle) than in MI (43 ± 1%). While the MI group exhibited parallel elongation of the infarcted (31.6 ± 3.8% increase) and reminiscent ventricular portions (33.5 ± 3.7%), MNC therapy preserved the initial infarct length. Infarcted walls were thicker (979 ± 31 mm) in the MNC group than in the untreated group (709 ± 41 mm), also demonstrating an absence of infarct expansion. In the border zones, MNC led to increased capillary densities and capillary/myocyte ratios. The cardiac systolic function remained depressed in MI, but improved by 19 ± 5% in MI+MNC which reduced the incidence of pulmonary arterial hypertension (37.5% in MI and 6.25% in MI+MNC).


CONCLUSIONS
MNC therapy prevented the infarct expansion and thinning related to cardiac remodeling and was associated with an improvement of border zone microcirculation: as a result, MNC therapy reduced typical MI dysfunctional repercussions.
dos Santos
Leonardo
L
Cardiology Division, Department of Medicine, Federal University of Sao Paulo, Brazil, SP 04024-900, Brazil. leodossantos@hotmail.com
Santos
Alexandra A
AA
Gonçalves
Giovana A
GA
Krieger
José Eduardo
JE
Tucci
Paulo José Ferreira
PJ
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation / Q000379:methods / Q000473:pathology; D054059:Coronary Occlusion / Q000150:complications / Q000601:surgery*; D005260:Female; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D051381:Rats; D011917:Rats, Inbred Lew; D020257:Ventricular Remodeling / Q000502:physiology