Methods And Mechanisms

In cell transplantation, healthy cells are grafted into the diseased myocardium to elicit repair. Cells can be individual or aggregated and can be delivered either by direct injection into the myocardium or via the blood supply that feeds the myocardium. The potential utility of determined and stem cells for such a therapy have been studied. Cell transplantation studies have been primarily targeted to ischemic and segmental cardiomyopathies, as opposed to treating global, dilated cardiomyopathies. A general protocol for cell transplantation is as follows:

1. Isolate cells of a specific type (e.g., cardiomyocytes, bone marrow stem cells [BMSCs], embryonic stem [ES] cells, etc.) from a source.

2. Purify and perhaps grow larger numbers of the cells in the laboratory; cells can also be genetically manipulated or tagged at this stage.

3. Administer the cells to the patient with the injured myocardium (Fig. 1) (11).

4. Wait and allow the cells to repair injured heart tissue.

The exact mechanism by which implanted cells repair the myocardium remains unclear and probably depends on the cell type used. In general terms, the new cells could directly replace or stimulate healing in existing host tissue. As potential examples of the first mechanism, new cells would become functional as cardiomyocytes in the myocardium or as endothelial or smooth muscle cells in myocardial blood vessels. As possible examples of the second mechanism, cells might interact with host cells via secreted signals, cell-cell contact, or cellular fusion to initiate events that lead to repair or tissue remodeling.

The result of these interactions could include the recruitment of endogenous repair cells, the stimulation of angiogenesis to increase local blood supply, or the inhibition of programmed cell death in host cardiomyocytes. Transplanted cells might also attenuate the pathological remodeling processes associated with the progressive or neurohormonal remodeling commonly associated with heart failure. The mechanisms of repair are further obfuscated by the variety of cell types studied and, to some degree, by the attempts to engineer specific therapeutic properties into such cells.

Several criteria must be fulfilled for cell transplantation to be deemed a useful therapy (12), including the following: (1) feasibility of transplantation; (2) survival of implanted cells;

(3) vasculogenesis and angiogenesis through the cellular graft;

(4) proliferative capacity of the therapeutic cells; (5) electromechanical integration of the graft with the host heart; (6) convergence of the phenotype of the implanted cells to that of the host; and (7) contribution of graft to cardiac performance and clinical outcomes. The complexity of this endeavor is illustrated in Fig. 2 (13).

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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