Comparison of Intracardiac Cell Transplantation: Autologous Skeletal Myoblasts Versus Bone Marrow Cells

Abstract

Background-Multiple cell types are being proposed for cardiac repair, but side-by-side comparisons are lacking. We tested the hypothesis that intracardiac transplantation of autologous bone marrow-or skeletal muscle-derived progenitor cells improve regional heart function to a similar degree. Methods and Results-Thirty-nine New Zealand White rabbits underwent cryoinjury of the left ventricle and simultaneous hind limb bone marrow aspiration or soleus muscle biopsy. Both muscle and bone marrow cells were expanded in vitro. After 2 weeks, 10 8 skeletal muscle (SM group) or bone marrow-derived progenitor cells (BM group) were injected into the cryoinjured region (SM: nϭ12; BM: nϭ8). Medium alone was injected into the remaining animals (Control: nϭ16). Regional systolic function was measured using micromanometry and sonomicrometry at baseline, before, and 4 weeks after cell injection. Cell treatment resulted in a similar degree of improvement in a derivative of stroke work in the SM and BM groups (Pϭ0.0026 and Pϭ0.0085 versus Control, respectively). No significant difference was seen between BM and SM groups (Pϭ0.9). On histology, engrafted cells were found in all of the cell treated animals. Injected myoblasts formed myotubes or muscle cells throughout the scar that expressed slow and fast myosin heavy chain. A subset of bone marrow cells differentiated toward a myogenic phenotype, as indicated by expression of desmin and ␣-sarcomeric actin in the engrafted areas. Conclusion-Transplantation and myogenic differentiation of bone marrow-derived progenitor cells increased regional systolic heart function after myocardial injury to a similar degree as skeletal myoblasts.

Establishing Early Functional Perfusion and Structure in Tissue Engineered Cardiac Constructs

“…Another challenge for cell therapy is the lack of an appropriate extracellular environment to assist the retention of transplanted cells and the structural and biomechanical integration of the repaired region with the host tissue. 49,50 …”

Cardiac Muscle Engineering: Strategies to Deliver Stem Cells to the Damaged Site

“…Such negative results were ascribed to the inability of skeletal myoblasts to balance cell death and achieve complete electromechanical integration with the recipient myocardium. Finally, skeletal myoblast administration was reported to determine no enhancement in major cardiac adverse events and mild effects on left ventricular remodeling process [53,54]. More recently, final results from SEISMIC [Safety and Effects of Implanted (Autologous) Skeletal Myoblasts (MyoCell) Using an Injection Catheter] Trial, a phase II-a study encompassing 40 patients experiencing congestive heart failure and receiving percutaneous intramyocardial injection of autologous skeletal myoblasts, reported the feasibility and safety of this procedure without significant arrhythmogenic events recorded at 6-month follow-up with respect to control groups, although left ventricular ejection fraction did not result significantly improve.…”

Gene and Cell Therapy for Heart Failure

“…As explained by the pioneers of myoblast transplantation, Menasché (83) and Taylor (141), myoblasts are attractive candidates for cardiac cell transplantation for a number of reasons. Under the correct culture conditions, hundreds of millions of cells can be obtained from a small muscle biopsy.…”