P74Paracrine effects of stem cells on cardiac remodelling

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Abstract

Purpose of our study included assessment of paracrine effects of stem cell (SC) therapy on cardiac remodelling in patients with congestive heart failure (CHF) of different origin.

Methods

Overall 53 patients with CHF were enrolled in our study. Patients were divided into groups according to the SC/placebo (NaCl solution) delivery method: selectively percutaneously intracoronary or transendocardially into the regions of interest and transepicardially during open heart surgery based on the non-invasive/invasive methods of investigation. We applied autologous bone-marrow stem (BMS) cell progenitors CD133 + in the treatment of patients with CHF due to advanced coronary artery disease [CAD] (n = 27) and non-ischemic dilative cardiomyopathy patients (NICMP; n=26).

Results

Single isolated SC therapy with autologous CD133 + progenitors at average dosage 2mln, performed transendocardially, resulted in the significant reduction of left ventricular (LV) end-diastolic volume with moderate increase of ejection fraction in short-term follow-up (3-6 months) in patients with CHF due to CAD in comparison to placebo group. Alongside during this period was observed moderate reduction of perfusion defects in SC "treated" regions with viable myocardium according to single photon emission computed tomography. These positive changes eliminated in 1 year follow-up. Other main LV remodeling indexes such as myocardial mass and left atrial volume did not change in 3-6 months follow-up. In NICMP patients we observed no changes in any of LV remodeling indexes.

Results

In order to evaluate biochemical processes and paracrine effects of stem cells we performed enzyme-linked immunoelectrodiffusion assay of patients plasma samples for VEGF, bFGF, angiogenin, angiopoetins-1,2, MMP-9, PlGF, endostatin, TNF-α, SDF-1α and NT-proBNP levels before and after elective SC therapy. In NICMP patients at 14 days after single isolated transendocardial SC delivery we noted significant increase of SC homing factor SDF-1α plasma concentration, whereas in patients with ischemic CHF - significant decrease of PlGF (placenta growth factor) concentration in comparison with placebo group. There were no changes in plasma NT-proBNP levels in both groups.

Conclusions

SC paracrine effects exerted transiently in ischemic scarred, but viable myocardium and did not exert in non-ischemic dilated myocardium. Thus isolated transendocardial delivery of BMS progenitors CD133 + at average dosage 2mln can have positive effects if it is repeated in 6 months after first delivery in patients with ischemic cardiomyopathy.

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