A Randomized Comparative Study on the Efficacy of Intracoronary Infusion of Autologous Bone Marrow Mononuclear Cells and Mesenchymal Stem Cells in Patients With Dilated Cardiomyopathy

Abstract

SummaryStem cell therapy has shown therapeutic benefit in dilated cardiomyopathy (DCM), but doubt remains about the most appropriate stem cell subpopulation. The current study compared the efficacy of intracoronary administration of bone marrow mononuclear cells (BMMC) or mesenchymal stem cells (BMSC) in patients with DCM.Fifty-three patients with DCM and reduced (< 40%) left ventricular ejection fraction (LVEF), were randomized to intracoronary infusion of BMMC (BMMC group, n = 16) or BMSC (BMSC group, n = 17) or equal volume normal saline (CTRL group, n = 20). LVEF, New York Heart Association (NYHA) class, left ventricular end-diastolic diameter (LVEDd), and myocardial perfusion were assessed at baseline and at 3-month and 12-month follow-ups. Major adverse cardiovascular events (MACE) were also recorded.At the 3-month follow-up, LVEF, NYHA class, and myocardial perfusion had improved significantly in the BMSC group (P = 0.004, 0.020 and 0.019, respectively) along with significant changes in LVEF and NYHA class in the BMMC group compared with CTRL (P = 0.042 and 0.047, respectively), however, LVEDd remained unchanged. In comparison with CTRL, LVEF, NYHA class, and myocardial perfusion improved significantly in the BMSC group at the 12-month follow-up (P = 0.005, 0.050 and 0.038 respectively), but not in the BMMC group (P > 0.05). There were no significant differences between the transplantation groups during follow-up (P > 0.05). There were no differences in MACE among the 3 groups (P = 0.817).Intracoronary bone marrow stem cell transplantation in DCM is safe and effective, while BMSC and BMMC infusion possess comparable effectiveness. (Int Heart J 2017; 58: 238-244) Key words: Heart failure, Therapeutics, Cytological techniques, Transplantation D ilated cardiomyopathy (DCM), characterized by ventricular dilatation and impaired systolic function of the left or both ventricles of incompletely understood pathogenesis, is the most common form of non-ischemic cardiomyopathy.1,2) Current therapies for the condition, such as beta-blockers, angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor antagonists (ARBs), and mechanotherapy seek to reduce the rate at which myocardial damage accrues but do not have regenerative potential. Thus, new therapeutic procedures for this condition are required for this significant, unmet clinical need.The exploration and development of regenerative treatment constitutes a promising therapeutic option for nonischemic cardiomyopathy.3,4) Intracoronary administration of autologous bone marrow stem cells (BMC) has proved to be safe and has shown significant improvement of cardiac function in the treatment of post-infarct and chronic ischemic models in both preclinical and clinical settings. [5][6][7][8] Because severely reduced coronary flow reserve and impaired microvascular function have been observed in patients with DCM, 9,10) several clinical studies have applied cell therapy to these patients, 4,[11][12][13][14] despite much controversy concerning the underlying mech...

Efficacy of mesenchymal stem cell therapy in systolic heart failure: a systematic review and meta-analysis

“…As shown in Table 1, all nine studies were randomised controlled trials, four [5, 11–13] of which were double-blind trials; two [17, 19] were single-blind trials, and three [14–16] did not show the blind method. A total of 612 patients with HF were included, of which 263 and 304 underwent MSC and placebo treatment, respectively.…”

“…Forty-five patients from one study [19], who underwent mesenchymal precursor cells (MPC) treatment, were also enrolled, because MPC shares many of the same phenotypic features as MSCs [20]. Among these studies, the origins of MSCs are varied: from autologous bone marrow in six studies [5, 11, 12, 14, 16, 17], from allogenic bone marrow in one study [19] and from allogenic umbilical cords in two studies [13, 15]. MSCs were delivered by intracoronary injection in three studies [14–16], by transendocardial stem cell injection (TESI) in four studies [5, 11, 12, 19] and by peripheral intravenous injection in two studies [13, 17].…”

Cell therapy with intravascular administration of mesenchymal stromal cells continues to appear safe: An updated systematic review and meta-analysis

“…The occurrence of thrombotic or thrombo-embolic events were reported in a total of 24 RCTs (n = 1112 patients) [20,21,26,29,32,33,37,40,50,56,58,60,63,66,69,70]. In the pooled analysis there was no significant increase in the risk of thrombotic/thrombo-embolic events for MSCs as compared to the control group (RR = 1¢14, 95% CI = 0¢67À1¢95, I 2 = 0%; see Fig.…”

Cigarette Smoking Impairs Adipose Stromal Cell Vasculogenic Activity and Abrogates Potency to Ameliorate Ischemia

“…Multiple clinical trials have suggested that cell-based treatments offer viable therapeutic approaches across a variety of pathological conditions [60, 61]. A majority of the trials evaluated the effects of locally or systemically delivered bone marrow MSC [4, 62, 63] as well as endothelial progenitor cells [64, 65] and ASC [60]. At the same time, growing recognition of the negative influence of aging [66–68], diabetes [69], and various environmental exposures [38, 70] on the biology of stem/progenitor cells prompts evaluation of the impact of these factors on the therapeutic potential of regenerative cells.…”