Global Contractility Increment in Nonischemic Dilated Cardiomyopathy after Free Wall-Only Intramyocardial Injection of Autologous Bone Marrow Mononuclear Cells: An Insight over Stem Cells Clinical Mechanism of Action

Abstract

Bone marrow mononuclear cells (BMMC) effects have been investigated in small series of nonischemic dilated cardiomyopathy (NIDC). Left ventricular myocardial contractility improvements occur, but doubt remains about their mechanism of action. We compared contractility changes in areas treated (free wall) and nontreated (septal wall) with BMMC, in selected patients who have showed significant ventricular improvement after free wall-only intramyocardial stem cells injection. From 15 patients with functional class III/IV (NYHA) and LVEF inferior to 35%, who received 9.6 ± 2.6 × 10(7) BMMC divided into 10 points over the left ventricular free wall, 7 (46.7%) showed LVEF relative improvement greater than 15%. Those patients were selected for further contractility study. BMMC were collected from iliac bone and isolated with Ficoll-Hypaque. Magnetic resonance imaging was used to measure the systolic thickening of the septal (nontreated) and free wall (treated) before injection and 3 months postoperatively. Mean systolic septal wall thickening increased from 0.46 to 1.23 mm (an absolute 0.77 ± 1.3 mm and relative 167.4% increase) and in the free wall from 1.13 to 1.87 mm (an absolute 0.74 ± 1.5 mm and relative increase of 65.5%). There was no difference in the rate of absolute or relative systolic thickening between the two walls (p = 0.866 and 1.0, respectively), when cells were injected only in the left ventricular free wall. BMMC transplantation in nonischemic dilated cardiomyopathy can improve ventricular function by an overall effect, even in areas that are not directly injected. This finding favors the existence of a diffuse mechanism of action, rather than a local effect, and should be reminded when the pathophysiology of stem cells is considered.

Intracoronary Transplantation of CD34+ Cells Is Associated With Improved Myocardial Perfusion in Patients With Nonischemic Dilated Cardiomyopathy

“…This was also observed in the study by Beeres et al 24 The study by Sant'anna et al in DCM also suggests that the effects of stem celledirected therapy in terms of contractile improvement were not limited to the area of injection but more diffuse in nature, suggesting a more diffuse mechanism of action rather than a local effect. 25 In a preclinical model of DCM, stem cell transplantation has been shown to improve cardiac function not only through induction of angiogenesis, but also by means of their ability to supply large amounts of angiogenic, antiapoptotic, and mitogenic Values are presented as mean 6 SD or n (%).…”

Comparison of Transendocardial and Intracoronary CD34 + Cell Transplantation in Patients With Nonischemic Dilated Cardiomyopathy

“…9 Similarly, direct transthoracic IM injection of bone marrow mononuclear cells has been associated with global contractility increment in patients with DCM. 10 At this time, it remains uncertain whether transendocardial stem cell delivery in patients with DCM is associated with greater retention and improvement in ventricular function than intracoronary delivery. To resolve this question, in this study, we sought to determine whether transendocardial stem cell delivery is associated with a greater retention rate and clinical improvement than intracoronary stem cell delivery in patients with DCM.…”

Safety and Efficacy of Intramyocardial Implantation of Peripheral Blood Stem Cell for Cardiomyopathy

“…15,16 The research results on outcomes of stem cell injection for DCM were limited. [17][18][19][20][21][22] Roura S, et al, demonstrated defective vascularization and impaired vasculogenesis (the de novo vascular organization of mobilized endothelial progenitors) and angiogenesis in dilated cardiomyopathy patients. The defective vascularization was associated with reduced myocardial expression of vascular β-catenin, an important angiogenic regulator.…”