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IL–3 effects on the regenerative inductive activity of bone marrow hematopoietic stem cells in experimental myocardial infarction

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PDF, Volume IV, №4, 2009

Belyaev N.N.¹, Rysuly M.R.², Isabekova A.S.¹, Severova E.A.², Pominova N.M.², Enin E.A.³, Perfil’eva Yu.V.¹, Supniyazova T.A.¹, Tleulieva R.T.¹, Izakhunova E.A.¹, Sereda E.N.², Fedotovskikh G.V.³, Denisov Yu.D.²

1. the M.A. Aitkhozhin Institute of Molecular Biology and Biochemistry, Almaty, Kazakhstan
2. the Research Institute of Cardiology and Internal Medicine, Almaty, Kazakhstan
3. the National Scientific Center for Surgery, Almaty, Kazakhstan

Keywords:
hematopoietic stem cells, IL-3, myocardial infarction

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The research was aimed to investigate the effects of stimulating bone marrow hematopoietic stem cells CHSCsJ when culturing ex vivo by cytokines to improve their regenerative properties in an experimental myocardial infarction. White outbread mice of both sexes were used in the experiments. Small-focal myocardial infarction was modeled by intraperitoneal introduction of isoproterenol, a p-adrenoceptor agonist. HSC CD 117+ were isolated from the bone marrow fraction with the buoyant-density of 1,09 g/ ml by employing immunomagnetic separation and cultured for 48 hours in the presence of IL-3. Thereafter the CXCR4 receptor expression and TGFfi production were assessed with an enzyme multiplied immunoassay. IL-3 stimulated hematopoietic stem cells were labeled by a fluorescent dye CCFSEJ and were introduced intravenously into animals with a small-focal myocardial infarction. A post-infarction production of the homing factor SDF-1 within the cardiac muscle, the migration of labeled HSCs into the cardiac tissue and histomorphologic alterations of a regenerative character were evaluated. 11-3 has been stated to enhance reliably the CXCR4 expression and TGFfi production when cultured for three days. At the 7-th day after an administration of isoproterenol there was a tendency towards increasing a production of the homing factor SDF-1 within the cardiac muscle, which disappeared as the myocardial infarction progressed. Isoproterenol-induced localization and the character of alterations within the mouse myocardium morphologically corresponded to a small-focal myocardial infarction. A histomorphologic assay demonstrated processes of reparative modeling of the myocardium and neoangiogenesis to be enhanced in case of introducing stimulated hematopoietic stem cells. The experiments performed indicate that new approaches to reenforce potential regenerative properties of hematopoietic stem cells of bone marrow are promising in the treatment of acute myocardial infarction.

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