The heart has its own reservoir of stem cells. These cardiac stem cells (CSCs) can be easily harvested from the heart, grow in culture, and then re-injected into heart after a heart attack to improve the structure and function of the heart.
However, what would it take to simply get CSCs to move from their present location to the damaged area without any invasive procedures? A chemical called “stromal cell factor-1alpha (SDF-1alpha) attracts stem cells to it. Stem cells have a receptor on their surfaces (CXCR4 for those who are interested), and when those receptors bind SDF-1alpha, stem cells move towards the source of SDF-1alpha. Therefore, some enterprising scientists from the Third Military Medical Hospital University, from Chongquing, China have overexpressed SDF-1alpha in the damaged region of the heart. Their results have shown that not only do CSCs move to the site of injury, but the size of the infarct shrinks without surgery.
In their first experiment, Kui Wang and co-workers from the laboratory of Lan Huang isolated heart tissues from mice and the stem cells migrated onto the culture plates. When these migrating cells were isolated, they expressed genes that are common the stem cells (c-kit and sca-1). These stem cells also expressed a whole host of heart muscle-specific genes, which confirms that they are definitely heart-based stem cells.
In the next experiment, Huang’s group exposed these isolated CSCs to cells that were expressing SDF-1alpha. The CSCs migrated toward the SDF-1alpha source with abandon. Also, they discovered some inhibitors that prevent CSC migration. These inhibitors prevent activation of a pathway called the PI3K pathway. This shows that the activation of PI3K pathway is the reason the stem cells become activated and move toward SDF-1alpha.
The final experiment involved inducing heart attacks in mice and then engineering the damaged portions of the heart to express SDF-1alpha with viruses. In response to this, CSCs migrated to the damaged area and made new heart muscle. The damaged area in the heart shrunk and the hearts functioned more effectively. Unsurprisingly, the inhibitors that prevented CSC migration in the test-tube assays, also prevented CSC migration to the site of damage in mice. Thus, CSC migration is also dependent on the activation of the PI3K pathway.
This paper shows that the PI3K pathway is the main way cells get their signal to migrate. Secondly, it shows that engineering damaged sites in the heart can recruit CSCs to the site and stimulate their healing activities. While this is an animal study, it sets a template for future clinical studies in heart attack patients.