Recovery of Regional but Not Global Contractile Function by the Direct Intramyocardial Autologous Bone Marrow Transplantation

Abstract

Background-Recent trials have shown that intracoronary infusion of bone marrow cells (BMCs) improves functional recovery after acute myocardial infarction. However, whether this treatment is effective in heart failure as a consequence of remodeling after organized infarcts remains unclear. In this randomized trial, we assessed the hypothesis that direct intramyocardial injection of autologous mononuclear bone marrow cells during coronary artery bypass graft (CABG) could improve global and regional left ventricular ejection fraction (LVEF) at 4-month follow-up. Methods and Results-Twenty patients (age 64.8Ϯ8.7; 17 male, 3 female) with a postinfarction nonviable scar, as assessed by thallium (Tl) scintigraphy and cardiac magnetic resonance imaging (MRI), scheduled for elective CABG, were included. They were randomized to a control group (n ϭ10, CABG only) or a BMC group (CABG and injection of 60.10 6 Ϯ31.10 6 BMC). Primary end points were global LVEF change and wall thickening changes in the infarct area from baseline to 4-month follow-up, as measured by MRI. Changes in metabolic activity were measured by Tl scintigraphy and expressed as a score with a range from 0 to 4, corresponding to percent of maximal myocardial Tl uptake (4 indicates Ͻ50%, nonviable scar; 3, 50% to 60%; 2, 60% to 70%; 1, 70% to 80%; 0Ͼ80%). Global LVEF at baseline was 39.5Ϯ5.5% in controls and 42.9Ϯ10.3% in the BMC group (Pϭ0.38). At 4 months, LVEF had increased to 43.1Ϯ10.9% in the control group and to 48.9Ϯ9.5% in the BMC group (Pϭ0.23). Systolic thickening had improved from Ϫ0.6Ϯ1.3 mm at baseline to 1.8Ϯ2.6 mm at 4 months in the cell-implanted scars, whereas nontreated scars remained largely akinetic (Ϫ0.5Ϯ2.0 mm at baseline compared with 0.4Ϯ1.7 mm at 4 months, Pϭ0.007 control versus BMC-treated group at 4 months). Defect score decreased from 4 to 3.3Ϯ0.9 in the BMC group and to 3.7Ϯ0.4 in the control group (Pϭ0.18). Conclusions-At 4 months, there was no significant difference in global LVEF between both groups, but a recovery of regional contractile function in previously nonviable scar was observed in the BMC group.

A comprehensive study on optimization of proliferation and differentiation potency of bone marrow derived mesenchymal stem cells under prolonged culture condition

“…The second important disadvantage of BMSC is that the proliferation and differentiation capacity of MSC declines with age, reducing their therapeutic potential (Stolzing et al 2008). Additionally, low frequency of mesenchymal stem cell creates a threat for cell migration and engraftment (Kuethe et al 2004;Wagner et al 2005;Hendrikx et al 2006).…”

Cardiac Effects of Experimental Intravenous Bone Marrow Cell Transplantation after Myocardial Infarction

“…5,6) Different bone marrow cells types have been used commonly after selection and cultivation. 10,11) CD133 + cells were probably most frequently used and proofed to be efficient. However, preparation of these cells is very time and cost intensive.…”

Stem Cell Therapy for Heart Disease

“…79 Some trials did not show significant results, 76,85 while others demonstrated benefits, but no effect on EF. 66,67,74,77,80,84,86 A highly anticipated trial, FOCUS-CCTRN, assessed BMC via transendocardial injection in chronic HF. However, results indicated no significant change in endpoints.…”