Skeletal Myoblast Cell Sheet Implantation Ameliorates Both Systolic and Diastolic Cardiac Performance in Canine Dilated Cardiomyopathy Model

Abstract

BackgroundImproving both systolic and diastolic function may be the most important factor in treating heart failure. In this study, we hypothesized that cell-sheet transplantation could improve these function in the damaged heart.MethodsWe generated a dilated cardiomyopathy model in beagles by continuous ventricle pacing at 240 beats per minute. After 4 weeks, the beagles underwent skeletal myoblast cell sheet transplantation (SMCST) or a sham operation, and rapid ventricle pacing continued for an additional 4 weeks. Six of the e8 beagles treated by SMCST were still alive 4 weeks after the procedure. We evaluated SMCST's cardiotherapeutic effects by comparing beagles treated by SMCST with beagles that underwent a sham operation (control, n = 5).ResultsDiastolic function, as well as systolic function improved significantly in the SMCST group as compared with the sham group (control vs SMCST group, median [interquartile range]: E/E', 16 [0.9] vs 11 [1.0]; P < 0.001; tau, 47 [6.0] vs 36 [4.4] ms: P = 0.005. Ejection fraction, 22 (6.0) versus 46 (7.5) %, P < 0.001; end-systolic elastance, 2.5 (0.4) versus 8.2 (3.5) mm Hg/ml, P = 0.001). Histological examination revealed that the volume of collagen I and the collagen I/III ratio in the myocardium were significantly higher in the control than that in the SMCST group (collagen I, 6.0 [0.8] vs 2.6 [1.3]; P = 0.006; collagen I/III ratio, 4.8 [1.7] vs 1.2 [0.4]; P = 0.010).ConclusionsThe potential of SMCST to ameliorate both systolic and diastolic performance was proven. The SMCST may be an alternative therapy of conventional medical treatment in the dilated cardiomyopathy heart.

Bone marrow‐derived mononuclear cell therapy for nonischaemic dilated cardiomyopathy—A meta‐analysis

“…As a potential therapeutic approach, cell‐based therapies have rapidly emerged. Different cell strains used include bone marrow mononuclear cells (BMMCs), G‐CSF‐stimulated autologous CD34 + peripheral blood stem cells (PBSC), embryonic stem cells (ESCs), skeletal myoblast, mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), cardiac stem cells and adipose tissue‐derived stem cells, either with the methods of intracoronary (IC) or intramyocardial (IM) injections. Among these cell‐based therapies, bone marrow‐derived mononuclear cells (BMMNCs) are easily obtained and cultured with differentiation capacity .…”

Long-term outcome of a dilated cardiomyopathy patient after mitral valve surgery combined with tissue-engineered myoblast sheets—report of a case

“…Heart failure, especially due to DCM, features disease pathologies such as fibrosis, myocyte apoptosis, and ischemia [13], and a treatment target for DCM should focus on the damaged myocardium in addition to the valvular disease. Several recent papers reported that myoblast sheets applied to ischemic cardiomyopathy tissue [4, 14] could heal old myocardial infarction (OMI) [15, 16] or DCM [17, 18] in large or small animal models through potent angiogenesis, anti-fibrotic effects, and stem cell recruitment induced by cytokine paracrine effects. Here, we applied this innovative method to a patient in whom pulmonary hypertension was successfully controlled by MVR, to improve the damaged myocardium and maintain it after surgery.…”

Arrhythmogenic risks of stem cell replacement therapy for cardiovascular diseases

“…Because these cells are of autograft origin, easy to extract and multiply, lack carcinogenic risks, and show wide tolerance to ischemia and excellent intrinsic contractility characteristics, autologous SkMs were the earliest candidates in clinical studies for myocardial repair (Menasche et al, 2003; Smits et al, 2003). It has been demonstrated that SkMs partially survive after being transplanted into infarcted myocardial tissue and improve LV function (inhibit LV dilation, increase contractility, and EF) and reverse LV remodeling (Saito et al, 2012; Shirasaka et al, 2016). SkMs ectopically expressed either serine/threonine kinase 1 (Akt‐1) or placental growth factor significantly enhance cardiac function and ventricular remodeling in infarcted heart (Gmeiner et al, 2011; Siepe et al, 2011).…”