Stem cell research might be the key to treating heart disease.
Researchers at University of Wisconsin, University of Alabama at Birmingham and Duke University are developing “heart patches” — collections of fabricated heart cells — that will be used to mend unhealthy hearts.
Teams from the three universities were awarded an $8.6 million grant by the National Institute of Health in September, which will allow them to create and study the application of stem cells as “heart patches” in large animals to treat heart disease.
Timothy J. Kamp, UW cardiologist and co-director of the UW Stem Cell and Regenerative Medicine Center, said heart disease often develops after a patient suffers a heart attack.
Because the heart can’t properly regenerate muscle after a heart attack, Kamp said existing muscle is replaced by scar tissue that isn’t capable of contracting. If the tissue can’t contract, it can’t contribute to the mechanical function of the heart.
According to the Centers for Disease Control and Prevention, heart disease is the leading cause of death for both men and women in the United States.
While this grant is funding the use of tissue engineering principles to create “heart patches” in animal models, Kamp said he hopes this seven year grant will produce something viable to test in humans.
In the past, Kamp said stem cells have individually been connected to the heart, but this method has seen only mild success.
Instead of single cells, these “heart patches” will be several million cells coupled together to create fully formed contracting pieces of heart tissue that are a few centimeters in diameter in both directions.
“These are things that you could easily see in the palm of your hand,” Kamp said.
For this grant, researchers at each university are addressing the different challenges to create a fully functioning “heart patch.”
UW researchers will create the three different types of cells needed to build a working patch of heart tissue, which include cardiomyocytes, or the cells responsible for muscle contraction; fibroblasts, the cells that give tissue structural framework; and endothelial cells, the cells that line blood vessels.
The team at Duke will take the cells fabricated at UW and format them into the appropriate combinations to generate a beating tissue.
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These working “heart patches” will then be sent to the researchers at Alabama to be tested in animal models. Kamp said it will likely take a multitude of combinations to identify those versions of heart patches capable of syncing up mechanically as well as receiving the electrical pulse of the surrounding tissue in the existing heart, which Kamp acknowledged is one of the largest hurdles of the grant.
“You have to remember the heart, it’s not like plugging in a USB drive to your computer,” Kamp said. “There’s no easy ‘plug and play’ option. This tissue is tricky business to get it to electrically couple and mechanically couple into the heart.”
Beyond manipulating the implanted tissue to couple with the existing heart muscle, Kamp said they need to ensure that once a “heart patch” has been successfully grafted onto a model, the receiving heart won’t reject it.
To prevent rejection, a second team of researchers at UW will work on the human immune response to these “heart patches.”
“[Right now,] we’ve got beating tissue, but we’ve got to get it into the heart and integrate it so it works well and that’s one of our big challenges,” Kamp said.
A lab at UW run by William Burlingham in the School of Medicine and Public Health’s Department of Surgery will work with mice whose immune systems have been replaced with human ones to determine if the cells and tissues used in the study will be able to be accepted by the human immune system.
Regarding the body’s immune response, Burlingham said he and his team are predominantly concerned with how T cells will receive the “heart patches.” In traditional organ transplants, Burlingham said T cells, which are a type of white blood cell, tend to be responsible for the body’s rejection of transplanted tissue.
The goal is to test the “heart patches” in mice with modified immune systems to find combinations where the T cells don’t recognize the heart cells as foreign.
By testing the tissues that the other teams develop through the course of the grant, Burlingham said his team’s results will potentially inform adjustments to improve the “heart patch.”
Kamp said while it’s one thing to have ideas and hypothesis to test, but it’s an entirely other thing to show that they actually work, he’s optimistic that they’re going to get there, even if that accomplishment is years away.
“I think it’s exciting to see things progressing,” Kamp said. “We’re getting better and better at making actual heart tissue in the laboratory and hopefully we’re now getting to the stage where this can really impact patients.”