Dr. Nadal-Ginard was convinced the cells were the product of stem cells arising in the body's bone marrow, circulating to the heart, and differentiating into the various cardiac cell types needed to regenerate the myocardium. His presentation showed two types of new evidence that myocardium-regenerating cells exist in the bone marrow and are able to differentiate into bona fide cardiac cells and coronary vessels. These findings, he told the multi-disciplinary scientists gathered at the meeting, open the possibility for development of true restorative therapies following heart attack and other cardiovascular diseases.
Until recently, scientists and clinicians believed that the heart had no self-renewal capability. That perception has "straight-jacketed" cardiovascular research, says Dr. Nadal-Ginard. Scientists reasoned that if no new myocytes could be generated in adult hearts, then all therapeutic interventions had to focus on preserving the heart cells remaining after the destruction of heart attack or simply the wear and tear of age or physiological or pathological stress. Furthermore, if no new myocytes were being generated, that by definition meant all the body's heart muscles had to be the same age. That would mean, for example, a 90-year-old man had nothing but 90 year old heart muscles.
Fortunately, says Dr. Nadal-Ginard, this view is changing. He reported two new studies supporting the fact that cells with stem cell characteristics reside in the adult myocardium or heart muscles.
First, he and his colleagues demonstrated that single stem-like cells isolated from the adult heart ventricular myocardium can differentiate, both in and outside the body, into the three major cardiac cell types. When the progeny of these cells are placed into a heart that has suffered muscle loss following an infarct, the cells begin to reconstitute a functional myocardium. Those are the properties one would expect of a cardiac stem cell, he says: self-renewal, multipotency or the ability to become different cells, and clonogenicity, the ability to keep producing the exact same cells needed once placed into the body.
A second proof that cells with stem cell characteristics reside in the adult myocardium is the fact that it is possible to mobilize and activate the cardiac resident stem cells by stimulating them with cytokines, naturally occurring chemicals involved in growth. When cytokines were injected near an area of dead heart muscle cells caused by an infarction, a population of primitive cells rapidly moved to the border zone of the infarct, and began to differentiate into myocytes, endothelial and smooth muscle vascular cells, regenerating a functional myocardium.
Dr. Nadal-Ginard concludes that the presence of stem cells in the myocardium, either as a resident population of embryonic origin or as a blood-borne population that continuously seeds the tissue, points to a mechanism for the continuous renewal of heart and coronary vessel cells throughout the lifespan of the individual. It also provides, he says, the basis for an increase in myocardial mass in response to physiological and pathological demands. Although much still needs to be learned, the future looks brighter for new therapies to restore muscle and other heart cells.
(American Association of Anatomists)