Long-Term Efficacy of Myoblast Transplantation on Regional Structure and Function After Myocardial Infarction

Abstract

Background Transplantation (Tx) of skeletal myoblasts (SM) within an infarcted myocardium improves global left ventricular (LV) function, although a direct systolic effect remains controversial. Methods and Results Global and regional LV functions were studied in a sheep model (n=16) of infarction before (baseline), and 4 (M4), and 12 (M12) months after in-scar injections of autologous SM or culture medium (CM). LV end-diastolic volume (EDV), ejection fraction (EF), wall motion score (WMS), and systolic myocardial velocity gradient (MVG) across the scar were measured by echocardiography with tissue Doppler imaging. Parameters were similar at baseline between groups. At M4, Tx of SM reduced the postinfarction increase in EDV (72±8 versus 105±13 mL in the CM group, P <0.05) and the decrease in EF (48±5 versus 33±3% in the CM group, P =0.006) although it improved WMS (5.4±1.2 versus 13±2.2 in the CM group, P <0.01) and SMVG (0.60±0.13 versus –0.04±.13 seconds -1 in the CM group, P <0.05). Results were similar at M12. In-scar accumulation of myotubes and SM were detected in all Tx animals up to M12, with co-expression of fast and slow isoforms of the myosin heavy chain (MHC) (30% of the fibers versus 0% in the normal skeletal muscle) and decreased collagen density (30±2% versus 73±3%, P <0.0001). Conclusion For up to 1 year, Tx of SM limits postinfarction EF deterioration and improves systolic scar function through colonization of fibrosis by skeletal muscle cells with expression of both MHC isoforms, which may confer to the graft the ability to withstand a cardiac-type workload.

Self-Healing Conductive Injectable Hydrogels with Antibacterial Activity as Cell Delivery Carrier for Cardiac Cell Therapy

“…Because of the expectation of these self-healing conductive hydrogels to be used in the cell delivery for cardiac repair, the cell delivery ability of this hydrogel was further investigated. H9c2 cells had been widely used in the regeneration of cardiac tissues. , Skeletal myoblasts had been demonstrated to have the ability to differentiate into myotubes or myocardium which was promising in improving cardiac function postinfarction. ,, Thus, C2C12 myoblasts and H9c2 cardiac myoblasts were chosen to measure the cell delivery ability of the hydrogels. It was tested for 7 days and the delivered cell numbers were monitored every day.…”

“…29,60 Skeletal myoblasts had been demonstrated to have the ability to differentiate into myotubes or myocardium which was promising in improving cardiac function postinfarction. 8,9,61 Thus, C2C12 myoblasts and H9c2 cardiac myoblasts were chosen to measure the cell delivery ability of the hydrogels. It was tested for 7 days and the delivered cell numbers were monitored every day.…”

“…Cell therapy has been developed as a promising strategy to protect and regenerate myocardial tissue during or after MI by delivery of appropriate types of cells to the MI area . Many types of cells have been used in the cell therapy for MI, among which stem cells , and skeletal myoblasts − are most widely used. The fraction size and fibrosis will be reduced by implantation of a certain amount of bone marrow stem cells .…”

Autologous intramyocardial injection of cultured skeletal muscle-derived stem cells in patients with non-acute myocardial infarction

“…It has been demonstrated both in large and small animal models that these cells engraft, differentiate into skeletal fibers, acquire certain characteristics of cardiac muscle and contribute to improve cardiac function and animal survival. 16,20,21,23 Very recent reports in patients with myocardial infarction have shown that skeletal autologous myoblast can survive after transplantation and form viable grafts in heavily scarred human myocardial tissue thus providing a proof of principle. 17,22,31 Although skeletal myoblast can be successfully transplanted, the percentage of cells that survive and differentiate into functional tissue is currently unknown and some reports suggest that it may be lower than 1%.…”

“…Injection of skeletal myoblast in animal models of myocardial infarction and more recently in humans has been associated with successful engraftment of skeletal muscle fibers, graft survival and functional benefit. 7,[14][15][16][17][18][19][20][21][22] Although controversial, some evidences suggest that skeletal muscle progenitors may acquire certain characteristics of cardiac muscle both in vitro and in vivo. 19,[22][23][24] We have examined, in a phase I clinical study, the feasibility and safety of intramyocardial transplantation of autologous skeletal myoblast cultured in vitro with autologous serum in patients with old myocardial infarction undergoing coronary artery bypass surgery.…”