Cardiovascular disease is the leading cause of death in Western countries. The damage that occurs during a heart attack results from the death and loss of the cells called cardiomyocytes that make up the majority of the myocardium. Medical therapy, balloon angioplasty, stent deployment, coronary artery bypass surgery, and heart transplantation are the current options available to the patient. However, with the exception of total heart transplantation, none of the therapies are able to replace the dead tissue with viable tissue. Cell transplantation has been suggested as a method to regenerate scarred myocardium.
The concept underlying cell therapy is that cells removed from a different part of the body can be transplanted into diseased tissue to restore decreased or lost function. Cardiac muscle is a good example for this approach since the remaining cardiomyocytes that survive following injury have an extremely limited ability to regenerate. Unlike cardiac muscle, skeletal muscle is capable of robust self-repair. The inability of cardiac muscle to self-repair is thought to be a consequence of the heart being deficient in a particular cell type called a myoblast. Myoblasts are small cells located between the basal lamina and sarcolemma in the skeletal muscle fiber. They respond to injury by extensive proliferation and can differentiate into nascent muscle, thereby providing a source for growth and repair. Myoblasts display a remarkable tolerance to reduced perfusion, making them a suitable choice for repair of ischemic heart disease. In particular, autologous skeletal myoblasts (ASM) are preferred since these are isolated from the same person into whom they will be later transplanted. This avoids many issues related to ethics and transplant rejection.
Autologous skeletal myoblast transplantation is not an approved therapy by the US Food and Drug Administration (FDA). Since it is considered an investigational new drug (IND), institutions participating in this type of human research must apply to the FDA for approval prior to screening for patients. In general, the acceptance criteria for entry into these studies require that patients have a documented previous myocardial infarction and an impaired left ventricular ejection fraction.
Autologous Skeletal Myoblast Isolation and Growth
The basic outline for ASM isolation and growth is as follows: a surgeon in a surgical suite makes an incision into the quadriceps muscle and aseptically removes a biopsy between 0.5g and 5g. The biopsy is placed in a transport solution and immediately taken to a tissue culture facility. Once inside a pre-irradiated laminar flow hood, the biopsy is removed and cut into small chunks approximately 1mm3 with sterile scissors.
- Dib N, et al., "Feasibility and safety of autologous myoblast transplantation in patients with ischemic cardiomyopathy", Cell Transplantation (2004), In Press.
- Herreros J, et al., "Autologous intramyocardial injection of cultured skeletal muscle-derived stem cells in patients with non-acute myocardial infarction", Eur. Heart J. (2003), 24 (22): pp. 2,012-2,020.
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- Menasche P, et al.,"Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction", J.Am Coll. Cardiol. (2003), 41 (7): pp. 1,078-1,083.
Crossref | PubMed
- Smits P C, et al., "Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up", J.Am. Coll. Cardiol. (2003), 42 (12): pp. 2,063-2,069.
Crossref | PubMed
- Dib N, et al.,"Long term follow-up of safety and feasibility of autologous myoblast transplantation in patients undergoing coronary artery bypass graft surgery", J.Am. Coll. Cardiol. (2004), 43 (5): p. 6A.