Heparin Enhances the Effects of Mesenchymal Stem Cell Transplantation in a Rabbit Model of Acute Myocardial Infarction

Behshid Ghadrdoost, Roya Khoshravesh, Nahid Aboutaleb, Abdolah Amirfarhangi, Somayeh Dashti, Yaser Azizi


Stem cell transplantation in combination with administration of bioactive compounds has shown promising results
in treating myocardial infraction (MI). In the current study, we investigated the effect of combining mesenchymal stem cells
(MSCs) transplantation with heparin into the infarcted heart rabbits. For this purpose, 35 male New Zealand white rabbits
were randomly divided into five groups: sham, MI, MI+ MSCs, MI+ heparin and MI+MSCs+ heparin. MI was induced by
30 min ligation of the left anterior descending coronary artery. The animals of MSCs and MSCs +heparin groups were
injected cell culture containing MSCs intramyocardially into the infarct area. Functional parameters of the left ventricle by
echocardiography, serum levels of VEGF by enzyme-linked immunosorbent assay, size of fibrotic area by Masson’s
trichrome staining, evaluation of morphology by Haematoxylin-Eosin and capillary density alkaline phosphatase staining
were compared between groups. Ejection fraction, fractional shortening and levels of VEGF significantly improved in MSCs
and MSCs + heparin group (P<0.05). The fibrotic area was significantly reduced (p=0.009) in MSC + heparin treated animals
in comparison with MSCs. Number of live cells and angiogenesis were increased significantly in MSCs + heparin groups in
comparison with MSCs (p< 0.05). Although injection of MSCs significantly restored normal function of fibrotic area, we
found that administration of heparin combined with MSCs to infarcted heart of animals could have better effects on LV
functional parameters in fibrosis area and resulted in superior therapeutic outcome in enhancing neovascularization and
improving cardiac fibrosis.

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