DAVID GRANOVSKY

NIH STARTS TO CATCH UP TO HEART DISEASE and STEM CELL TREATMENTS

In VICTORIES & SUCCESS STORIES on February 2, 2010 at 4:20 pm

For more info on clinical trials for treatment of heart disease, go HERE!

In the research laboratory, investigators often use a mouse or rat model of a heart attack to study new therapies (see Figure 9.1. Rodent Model of Myocardial Infarction). To create a heart attack in a mouse or rat, a ligature is placed around a major blood vessel serving the heart muscle, thereby depriving the cardiomyocytes of their oxygen and nutrient supplies. During the past year, researchers using such models have made several key discoveries that kindled interest in the application of adult stem cells to heart muscle repair in animal models of heart disease…

A second study, by Jackson et al. [3], demonstrated that cardiac tissue can be regenerated in the mouse heart attack model through the introduction of adult stem cells from mouse bone marrow. In this model, investigators purified a “side population” of hematopoietic stem cells from a genetically altered mouse strain. These cells were then transplanted into the marrow of lethally irradiated mice approximately 10 weeks before the recipient mice were subjected to heart attack via the tying off of a different major heart blood vessel, the left anterior descending (LAD) coronary artery. At two to four weeks after the induced cardiac injury, the survival rate was 26 percent. As with the study by Orlic et al., analysis of the region surrounding the damaged tissue in surviving mice showed the presence of donor-derived cardiomyocytes and endothelial cells. Thus, the mouse hematopoietic stem cells transplanted into the bone marrow had responded to signals in the injured heart, migrated to the border region of the damaged area, and differentiated into several types of tissue needed for cardiac repair. This study suggests that mouse hematopoietic stem cells may be delivered to the heart through bone marrow transplantation as well as through direct injection into the cardiac tissue, thus providing another possible therapeutic strategy for regenerating injured cardiac tissue.

More evidence for potential stem cell-based therapies for heart disease is provided by a study that showed that human adult stem cells taken from the bone marrow are capable of giving rise to vascular endothelial cells when transplanted into rats [6]. As in the Jackson study, these researchers induced a heart attack by tying off the LAD coronary artery. They took great care to identify a population of human hematopoietic stem cells that give rise to new blood vessels. These stem cells demonstrate plasticity meaning that they become cell types that they would not normally be. The cells were used to form new blood vessels in the damaged area of the rats’ hearts and to encourage proliferation of preexisting vasculature following the experimental heart attack.

Like the mouse stem cells, these human hematopoietic stem cells can be induced under the appropriate culture conditions to differentiate into numerous tissue types, including cardiac muscle [10] (see Figure 9.2. Heart Muscle Repair with Adult Stem Cells). When injected into the bloodstream leading to the damaged rat heart, these cells prevented the death of hypertrophied or thickened but otherwise viable myocardial cells and reduced progressive formation of collagen fibers and scars. Control rats that underwent surgery with an intact LAD coronary artery, as well as LAD-ligated rats injected with saline or control cells, did not demonstrate an increase in the number of blood vessels. Furthermore, the hematopoietic cells could be identified on the basis of highly specific cell markers that differentiate them from cardiomyocyte precursor cells, enabling the cells to be used alone or in conjunction with myocyte-regeneration strategies or pharmacological therapies. (For more about stem cell markers see Appendix E.i. How Do Researchers Use Markers to Identify Stem Cells?)

For more info on clinical trials for treatment of heart disease, go HERE!

more from NIH…

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