A Step toward Healing Broken Hearts with Stem Cells

The potential of stem cell therapy is huge–these potent cells have the ability to develop into just about any tissue type that exists, and many dream of using them for healing spinal cord injuries, reversing Alzheimer’s, and curing Parkinson’s. But while the idea is lovely in theory, stem cells are remarkably fickle and susceptible to chemical and physical cues that researchers are only just beginning to understand.

For instance, scientists have been trying to find a way to use embryonic stem cells to help mend injured hearts in the aftermath of a heart attack. The stiff, scarred muscle that results from oxygen deprivation can greatly decrease a heart’s ability to pump blood to the rest of the body, and the regenerative power of stem cells have long seemed a good solution. But early trials, in which experimenters simply injected the cells straight into the injured heart tissue, showed unexpected results: Rather than differentiating into healthy, beating cardiac cells, they instead took their cue from the hardened scar tissue and began developing into something more akin to bone.

Recent studies have suggested that part of the reason for this is that embryonic stem cells are incredibly susceptible to physical cues from their surroundings. A few years ago, bioengineer Adam Engler showed that when the exact same stem cells are placed on soft, medium, or hard substrates, they differentiate into brain-, muscle-, and bone-like cells, respectively. Even something as simple as the stiffness of their surroundings impacted the cells’ development.

Now Engler, a stem cell biologist at the University of California at San Diego, and graduate student Jennifer Young, have taken this research a step further. In a study they presented yesterday at the American Society for Cell Biology (ASCB) meeting in San Diego, Young and Engler studied embryonic chicken hearts with atomic force microscopy to determine how their stiffness changed during the two-and-a-half weeks post-fertilization. They created a matrix that closely replicated the stiffening rate, then placed embryonic chicken cardiac cells on it to see how they developed. Compared to cardiac cells grown on static gels, which remained developmentally stuck, those growing on the dynamic matrix showed remarkably similar markers to cells that developed inside the embryo itself.

“The hope, from a therapeutic standpoint, is that you could take the material with your stem cells and inject them together,” Engler says. “We would encapsulate the cells, inject them with the dynamic gel, and hope the gel would form in the [injured cardiac] tissues and provide the appropriate mechanical cues.”

Granted, the experiments are still in very early stages, and Engler and Young haven’t yet tried their matrix with human embryonic stem cells; that’s their next step. But just the knowledge that it might be possible to force embryonic stem cell differentiation with mechanical cues is a substantial advance. Of course, whether an injured heart would be able to incorporate this new tissue is another question altogether.

These videos show beating heart cells growing on a scaffold. In the first video, beating of chicken embryonic heart cells on stiff matrices, which exhibit scar-like rigidity, is impaired and the frequency great reduced.

Beating frequency is better maintained on matrices that closely mimic in vivo elasticity, such as shown in the below video.

Credit: Young and Engler, UCSD