An Experimental Study On The Effect On The Cardiac Cells After Self Bone Marrow Stromal Stem Cells' Transplantation In Congestive Heart Failure

OBJECTIVES: We conducted this study to evaluate the feasibility and cellular mechanism of self bone marrow stromal stem cells' transplantation in the experimental model of chronic end-stage congestive heart failure produced by right ventricular rapid pacing.METHODS: A small bone marrow aspirate was taken from the iliac crest of healthy swines and BMCs were isolated as previously described, then co-cultured with 5-aza at different concertration for 24hous. After cultured for additional 2 weeks, BMCs were identified by means of immuno- histochemistry technique. Heart failure was induced by rapid pacing(230bpm) in 15 swines over 4 weeks.Five animals enderwent self BMCs transplantation and 5 animals received CSCs transplantation by means of coronary injection while another 5 animals did not received additional treatment. In following 4 weeks both groups had a reduced rate(190bpm) of pacing designed to maintain heart failure. Two-dimensional echocardio- graphic studies were recorded at the time of baseline, 4 weeks pacing late and 4 weeks post-transplantation. The ratio of apoptosis in myocardial tissure was examined by means of Tunel in different times. We also tested the IGF- I and TNF- a level in serum to explore the mechanism of improve of cardiac fu nction after cellular transplantation.RESULTS: (1) A part of the cells induced by 5-aza had morphological changes and 29% of positive stained by Tn T. (2) BMCs and CSCs groups had significant sustained improvement in left ventricular ejection fraction and cardiac output to baseline, to pre-transplantation(all P <0.05).And there are significant reductions of. LVEDD and LVESD (all P <0.05) in BMCs and CSCs transplant groups. By the way, these changes were more obviously in CSCs group than that in BMCs group(all P <0.05).(3)Apoptosic ratio in myocardio was decreased in BMCs and CSCs groups (P<0.05) at 4 weeks laterafter stem cells transplantation. (4) Serum levels of IGF- I were significantly elevated in BMCs and CSCs groups (P<0.05) at 4 weeks later after stem cells transplantation whereas the levels of TNF- a were decreased step by step(P<0.05).CONLUSIONS: (1) The therapy of self Bone Marrow Stromal Stem cells' transplantation was effective, feasible and safe in chronic end-stage congestive heart failure. (2) The improvement of heart function were more obviously after CSCs transplantation than that in BMCs. (3) Stem cells' transplantation can restrain apoptosis in cardiac cells, accelerate secretion of IGF- I and the circadian thickening of myocardium. Further more it can reduce the level of TNF- α in serum by means of autocrine and paracrine.