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Oulun yliopiston väitöskirjat

STUDIES ON BONE MARROW-DERIVED STEM CELLS IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION, ACTA UNIVERSITATIS OULUENSIS D Medica 1089

ISBN-13:	978-951-42-9391-7
Kieli:	englanti
Kustantaja:	Oulun yliopisto
Laitos:	Lääketieteellinen tiedekunta
Oppiaine:	Lääketiede,farmasia
Painosvuosi:	2011
Sidosasu:	pehmeäkantinen
Sijainti:	Print Tietotalo
Sivumäärä:	154
Tekijät:	MIETTINEN JOHANNA

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Intracoronary administration of autologous bone marrow derived stem cells (BMC) has beenpostulated to repair the myocardial damage in patients who have suffered acute ST-elevationmyocardial infarction (STEMI). The aim of this study was to find determinants for the leftventricular functional recovery after BMC treatment of STEMI and to study the effect of BMCtreatment on different biochemical and clinical parameters associated with the outcome of STEMIpatients. In this study, STEMI patients treated with thrombolysis were randomly assigned to receiveeither intracoronary BMC (n=39) or placebo (n=39) into the infarct related artery at the time ofpercutaneous coronary intervention. The efficacy of the BMC treatment was assessed bymeasurement of the change of left ventricular ejection fraction (LVEF) from baseline to sixmonths after STEMI. Two-dimensional echocardiography was used to assess PA pressure, LVsystolic and diastolic function. Blood samples were drawn for biochemical determinations atseveral time points and BMCs were cultured in the laboratory for in vitro analyses. In the BMC group, the most powerful determinant of the change of LVEF was the baselineLVEF. Patients with baseline LVEF at or below the median (¡Ü62.5%) experienced a more markedimprovement of LVEF than those above the median. Elevated levels of N-terminal probrainnatriuretic peptide (NT-proBNP) and N-terminal proatrial natriuretic peptide (NT-proANP) werealso associated with an improvement of LVEF in the BMC group. However, no difference wasobserved between the BMC group and the placebo group in the changes of the levels of NT-proANP, NT-proBNP or any of the inflammatory markers measured. The BMC group showed atrend toward a reduction of peak PA pressure, while the placebo group had a significant increaseof peak PA pressure at 6 months. In addition, there was a greater improvement in the LV diastolicfunction, assessed in quartiles, in the BMC group. The in vitro studies of BMCs revealed thatexposure to tumor necrosis factor alpha (TNF-¦Á) significantly enhanced the proliferation of BMCsand resulted in activation of immunosuppression by altering the expression of severalimmunosuppressive proteins. In conclusion, low baseline LVEF as well as high levels of natriuretic peptides NT-proANPand NT-proBNP, which reflect the severity of the hemodynamic and neurohumoral reactionsevoked by the myocardial damage, have a considerable association to a better response to stemcell therapy after an acute STEMI. BMC therapy also prevents the increase of PA pressure andimproves the cardiac diastolic function. Based on in vitro studies, the inflammatory cytokine TNF-¦Á seems to evoke an enhanced proliferation of the bone marrow-derived mesenchymal stem cellsand activation of several immunosuppressive defence mechanisms.

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