Evaluation of the efficacy of granulocyte colony-stimulating factor for the treatment of experimental myocardial destruction in mice.

We studied the effects of recombinant granulocytic CSF on heart remodeling in BALB/c mice after cryodestruction. Administration of granulocytic CSF was started 1 day after cryodestruction (subcutaneously, 10 µg/kg/day, for 4 days). As early as after the first injection, leukocytosis in the peripheral blood started to develop, leukocyte count peaked on days 4-6 and returned to normal on day 14. Treatment with granulocytic CSF significantly increased the content of progenitor cells in the bone marrow and led to rapid development of the inflammatory reaction and myocardium infiltration with mononuclear cells. Injections of granulocytic CSF did not reduce scar area, but provided significantly less pronounced heart hypertrophy, which attests to its better functional properties. By day 30 after cryodestruction, control animals and animals receiving granulocytic CSF exhibited similar morphological picture at the site of damage. Thus, our regimen of granulocytic CSF administration produced a mobilizing effect on bone marrow progenitor cells and postinfarction heart remodeling. Direct effects of granulocytic CSF on the heart have to be established for its use in the treatment of myocardial infarction.

Comparative assessment of heart remodeling in rats after experimental coronary stenosis and cryodestruction.

Comparative analysis of myocardial changes due to heart remodeling after experimental coronary stenosis and cryodestruction in rats was performed. Similar picture of heart remodeling was observed in all animals on day 45 irrespective of the type of destruction: hypertrophy of intact myocardium of the left ventricle, formation of extensive connective tissue cicatrix, and similar structural changes in the myocardium adjacent to the damage area. The type of the damaging influence possibly plays a role at the stage of lesion formation. We concluded that the proposed method of cryodestruction induces heart remodeling comparable to that observed after coronary occlusion.

Effect of transplantation of bone marrow cells on morphology of rat myocardium after cryodestruction.

We studied the effects of bone marrow cell transplantation on myocardium of the prenecrotic zone in Wistar rats. Intramyocardial cell transplantation reduced the severity of hypertrophy of myocardium and the degree of its cicatricial degeneration on day 40 after cryodestruction. The morphology of the myocardium in the prenecrotic zone depended on the type of transplanted cells. The course of inflammation was swifter; vascularization of the myocardium was more intensive. The best effect, evaluated by the number of new vessels, was observed after MSC transplantation. Hence, the positive effect of bone marrow cell transplantation is realized at the expense of more rapid structural organization of the damaged site and stimulation of myocardial vascularization.

Colony-forming cells in rat myocardium after destructive exposure and intramyocardial transplantation of bone marrow cells.

The content of colony-forming cells in myocardial cell culture from the perinecrotic zone of rat heart was evaluated on day 40 after cryodestruction. The mean cellularity after cryodestruction was 12-fold lower than in intact animals. Intramyocardial transplantation of bone marrow cells (mononuclears, mesenchymal stem cells, and mesenchymal stem cells treated with 5-azacitidine) into the perinecrotic zone increased the content of colony-forming cells. After transplantation of mesenchymal stem cells and mesenchymal stem cells treated with 5-azacitidine, the number of colonies reached 33 +/- 7 and 11 +/- 3, the mean cellularity being 2975 +/- 80 and 1105 +/- 42 cells/cm2, respectively. Hence, intramyocardial transplantation of mesenchymal stem cells created an appreciable pool of colony-forming cells in the myocardial perinecrotic zone. Treatment with 5-azacitidine reduced survival of mesenchymal stem cells after intramyocardial transplantation.