Heal My Broken Heart

It was a heated, humid Sunday afternoon in a park within the bustling city of Singapore. The lush trees were swaying in the gentle wind and the grass was shining brightly through the pavement cracks. I was finally able to take some time off work to visit Grandma. She was lonely after Grandpa passed away, but that day she was upbeat and chatty. Suddenly, as we were resting on a bench, she heaved over in pain, clutching her chest, her breathing tightening at an alarming rate! I tried to calm her, but the tensing spread to her arms and back. I panicked and prepared to call emergency. Then abruptly, she sat up with her heartbeat normal again. Later in the hospital, I learned that Grandma experienced, and survived, a heart attack. Though I have been working on heart regeneration technologies, this was my first time witnessing a heart attack, or myocardial infarction.

The heart, one of the most vital organ in your body,  pumps 6 quarts of blood and makes 100,000 beats every 24 hours (Lewis). Yet, heart diseases and failures are the number one causes for deaths in the country yearly (Heidenreich). Diabetes, Coronary heart disease, and high blood pressure can damage your heart (“Heart Failure Fact Sheet”), and there are no cures. Heart attacks, like the one Grandma experienced, leave behind scar tissues on the heart and make it hard to pump. Many biomedical engineers like me tried injecting stem cells near the heart, in hopes that they would differentiate into cardiovascular muscles and replace the failing cells. However, heart improvements were diminutive and caused irregular heartbeats. Hence, we searched for other ways to recruit stem cells to the heart.

Instead of injecting stem cells, we tried attracting stem cells in the body’s bone marrow to migrate towards the heart, using a special protein. Interestingly, certain chemicals could activate bone marrow to make stem cells that become heart muscle cells, or cardiomyocytes (Geddes 80). Although clinical trials showed promising results, only a low percentage of bone marrow stem cells eventually grew into heart tissues. However, they appeared to be the catalyst for the proliferation of stem cells resident in the heart, which prompted us to work on regenerating these instead. 

Surprisingly, in an average 25 year old, one percent of heart cells are being replaced by stem cells that you are born with, but this capability declines as we age. In fact, a chemical called thymosin beta-4 can trigger the growth of heart muscles in young mice, from their heart stem cells located within the epicardium, the layer outside heart muscles. But somehow, thymosin beta-4’s effect is weak in adults, so this method is not viable in humans (Geddes 81). However, rather than triggering heart stem cells to grow, which take a long time (up to months) to differentiate into cardiomyocytes, why not make the heart muscle cells divide instead?  

Today, we are working on a very promising technology to improve heart health by having the heart heal itself. We first used mass spectrometry to search over 300 proteins, and find those that would promote the proliferation of cardiomyocytes. Only one protein, Follistatin-like 1 (Fstl-1), stood out. This special protein increases the cell growth signaling pathway when present in the epicardium, thus leading to the regeneration of cardiomyocytes. The challenge is then how to deliver this protein to the heart, so we bioengineer a patch fabricated with collagen and load it with Fstl-1 (Wei) (Vunjak-Novakovic 462). This patch attaches to the heart muscle to transport the protein, and unlike stem cell techniques, it isn’t consisted of cells, which means immunosuppressive drugs that disable the immune system to ensure acceptance of foreign tissues, are not needed. This lessens the chances of infection. Subsequently, the collagen gets absorbed into the epicardium and provides an enriching environment for muscle regrowth (White).

“You’ll be alright Grandma.” I leaned over the couch and held her hand. The doctor had prescribed nitroglycerin that expanded her valves, thus reducing strain on her heart. She was exhausted, but looked alert.

“We are working on an invention, a special patch that can be attached to the heart to make heart muscles grow and become stronger again,” I revealed.

“Wow, really? Does it work well?” Grandma perked up.

“Yes! It is more effective than other methods such as stem cells which take a long time. So far, trials on animals are amazingly successful,” I announced. We tested the patch on pig and rat hearts and found that more than half of the injured heart cells were re-grown and functional within weeks (Vunjak-Novakovic 462).

“But we need to ensure complete human safety and health by conducting many more tests on animals first. We need to be absolutely sure that there are no side effects, before human trials can begin,” I explained.

The challenges of altering cell growth signaling or gene expression of cardiomyocytes include possibilities of cancer. Hence the dosage amount of Fstl-1 protein needs to be carefully chosen to prevent any uncontrolled growth. In fact, our company is committed to the Biomedical Engineering Society Code of Ethics. We publish our findings accurately and responsibly, and use our knowledge to enhance the safety, health, and well-being of the public. We will proceed to license this technology only if all the human trials are successful. In addition, we also address environmental safety and sustainability concerns. Although collagen and Fstl-1 can be collected from living organisms such as cattle, pig, and fish, the proteins for this invention will be grown by artificial cells instead.

“But how will they put the patch inside the heart? Don’t they have to cut through your chest?” Grandma asked nervously.

“Yes, you’re right. Surgery is necessary and always risky. But I have an idea on how to improve this: we can inject the protein into the bloodstream and program a microbot to transport it to the heart. There it will release the protein on the heart muscle cells, and can avoid surgery entirely.” 

“Oh dear, you have such wonderful ideas!” She smiled.

Today, thousands of people are in need of heart transplants but the chances of survival are minuscule unless miracle donors appear. Now imagine in the near future, your doctor tells you instead that you just need to inject a microbot with a protein to help your heart muscles regenerate. The thousands of heart patients can just have their hearts heal themselves! No one would have the fear of dying on a waiting list. This is the future of regenerative technology, not only for the heart, but all other organs as well.

References:

Heidenreich, Paul A., et al. "Forecasting the Future of Cardiovascular Disease in the United States." National Center for Biotechnology Information. U.S. National Library of Medicine, 1 Mar. 2011. Web. 10 Nov. 2015. .

Geddes, Linda. "Heart, Heal Thyself." New Scientist The Collection Medical Frontiers 2.2 (2015): 78-81. Print.

"Heart Failure Fact Sheet." Centers for Disease Control and Prevention. 3 Dec. 2013. Web. 10 Nov. 2015. .

Lewis, Tanya. "Human Heart: Anatomy, Function & Facts." LiveScience. TechMedia Network, 7 Jan. 2015. Web. 8 Nov. 2015. < http://www.livescience.com/34655-human-heart.html>.

Vunjak-Novakovic, Gordana. "Cardiac Biology: A Protein for Healing Infarcted Hearts." Nature (2015): 461-62. Print.

Wei, Ke. "CIRM Scholar Ke Wei Talks Heart Regeneration." The Stem Cellar. 7 Oct. 2015. Web. 8 Nov. 2015. < http://blog.cirm.ca.gov/2015/10/07/cirm-scholar-ke-wei-talks-heart-regeneration/>.

White, Tracie. "Delivering Missing Protein Heals Damaged Hearts in Animals, Stanford-led Study Finds." News Center. 16 Sept. 2015. Web. 10 Oct. 2015. < http://med.stanford.edu/news/all-news/2015/09/delivering-missing-protein-heals-damaged-hearts-in-animals.html>.