Using Stem Cells to Repair the Heart after Myocardial Infarction

THE POTENTIAL RELATIONSHIP BETWEEN STEM CELLS AND MYOCARDIAL INFARCTIONS

A myocardial infarction, more commonly known as a heart attack, is when the heart’s oxygen supply is disturbed. Every cell in our body needs oxygen to survive and function. When the heart is “starved of oxygen for too long, a portion of the heart can die, never [reviving again]” [1]. The “lifeless [parts] of the heart are replaced by inflexible scar tissue not designed for pumping blood…forcing the remaining muscle [to] push itself to work harder” [1]. A myocardial infarction leads to heart failure due to the weakening of the heart. “Roughly half of patients diagnosed with the condition will not live more than five years after heart failure, especially due to research not yet leading to a cure” [1]. “Every year, 735000 Americans suffer a myocardial infarction” [2] and about “five million Americans currently experience heart failure” [1]. With the large number of people experiencing heart problems reported in the statistic coupled with the absence of a cure, something needs to be done to mediate this situation.

I am very passionate about finding methods which help reduce and treat people who have experienced a heart attack. The families of each of the five million Americans with heart failure need to be assured that something is being done to prevent these deaths. As a future bioengineer, I want to implement innovative methods that can potentially help the millions of people experiencing heart failure from myocardial infarctions. After researching potential solutions, I fell upon an innovation that can realistically be developed into a successful preventive measure for heart failure, only if enough engineers are behind it. It involves using stem cells to repair the weakened heart after a myocardial infarction.

“Stem cells can be found in the bone marrow, fat, blood, [and] embryonic connective tissue” [3]. Stem cells are “unique in their ability to develop into many types of cells” [3]. Stem cells have the potential to differentiate into heart cells, leading to the prospect of repairing the damage to the heart caused by a myocardial infarction. With stem cells being readily available in the body, we can research ways to inject stem cells to the heart and engineer the stem cells to develop into heart cells, in turn repairing the heart, and preventing heart failure.

More scientists and engineers should devote their time and resources to eradicating heart failure in the population. Even with studies proving stem cells’ abilities in repairing the heart, it is still not widely used for treatment. The scientific community supports this innovation and “in fact, the promise of stem cell therapy was recognized with the 2012 Nobel Prize in Physiology or Medicine” [3]. I hope stem cells offer a solution to people who suffer from a myocardial infarction to help get them proper treatment for their hearts.

HOW STEM CELLS WORK

The basic unit of life in the human body is the cell. All our organs, including the heart, are composed of cells. Cells come in many different types. For example, our heart has heart cells, our brain has brain cells, our bones have skeletal cells, et cetera. Our body’s cells regularly divide, essentially replenishing our old cells with newer cells. On the other hand, our heart cells do not regularly divide, hence the fact that once cells in the heart are damaged, they stay damaged. A damaged heart leads to heart failure, increasing the chance of early death.

This is where stem cells come into play. Stem cells have the “potential to develop into many different cell types…and [divide] essentially without limit to replenish other cells as long as the person or animal is still alive” [4]. “When a stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function” [4]. “Stem cells can give rise to specialized cells, such as heart muscle cells designed for pumping blood to the entire body, in a process called differentiations” [4]. During differentiation, “the cell goes through several stages, becoming more specialized at each step” [4]. It is understood that “internal signals are controlled by a cell’s genes…and external signals for cell differentiation include chemicals secreted by other cells, physical contact with neighboring cells, and certain molecules in the [surrounding area]” [4]. Really, signals sent to the stem cell trigger the stem cell to divide multiple times, becoming more specialized each time. If scientists and engineers can identify “specific sets of signals that promote differentiation into specific cell types” [4], then there lies the prospect of systematically using stem cells to engineer heart cells.

STEM CELL DELIVERY IN THE HEART

As of right now, there is no cure for heart failure or preventive measure after a myocardial infarction. Stem cells are the answer to repairing the heart. The use of bone marrow cells in “cardiovascular diseases, [like heart disease], has the advantage that bone marrow can be easily accessed, is renewable, and is an autologous, [coming from the same person], source for regenerative cells, [cells that regenerate into specialized cells like heart cells]” [5].

“For cell therapy, 80 to 250 mL of adult bone marrow blood is aspirated from the iliac crest, [a bone region of the pelvis], under local anesthesia, [a process of numbing the region]” [5]. The blood extracted from the iliac crest is full of bone marrow stem cells, the same cells that engineers hope they can differentiate into heart cells.

While extracting these stem cells from the patient’s body is simple, it is harder to decide which method to use to actually transplant the stem cells to the heart. A popular method is Direct Intramyocardial Injection; in this technique, the stem cells are injected directly into the damaged regions of the heart [6]. The drawback from this method is that the needle from the injection can cause “leakage and lead to massive loss of [the injected stem] cells” [6]. Another method used is Intracoronary Infusion, where stem cells are delivered into one of the heart’s arteries [6]. However, with this method, the injected stem cells may not be retained by the heart because the cells are not deposited near the epicenter of the damage [6]. Additionally, this method has caused myocardial microinfarctions, which are essentially minor heart attacks. The last method under discussion in the scientific community is a homing system, where specific chemical attractants in the injured tissue attract specifically engineered stem cells [6]. However, with this method, the majority of injected cells are washed out and do not survive long enough in the heart [6].

The problem associated with these methods is that there is a loss of stem cells after delivery. Bioengineers need to commit resources to developing a method to directly inject the stem cells into the heart, and keeping the stem cells contained in the region. A successful method would increase the percentage of specialized stem cells.

STEM CELLS WORKING TO SPECIALIZE INTO CARDIAC CELLS

Once the stem cells are delivered near the damaged areas of the heart, the regeneration of cardiac (heart) cells is possible. There is a lack of understanding on how or why specifically the stem cells turn into heart cells. “Recent studies indicated that the benefits associated with adult stem cell injection might come from paracrine effects, the effect of a nearby cell sending chemical and electrical signals to the stem cell, and not from myocardial differentiation” [6]. Studies showed that bone marrow stem cells “produce and secrete a broad variety of cytokines, chemokines, and growth factors, [all of which] promote cardiac repair [7]. These paracrine factors “influence adjacent cells and exert their actions” on the damaged cardiac cells [7]. It might be that the stem cells do not even differentiate into cardiac cells, but instead promote repair through exchanges of signals. “Recent work suggests that coupling of myocytes to adjacent cells, tissues, and extra-cellular matrix results in external cues that shape ventricular myocytes architecture” [8]. Basically, the surrounding heart cells connect with the stem cells to essentially form the shape of the original area of the heart. The cells “wrap around the ventricular cavities in the developed heart” [8]. The many therapies discussed “assume that the transplanted cells will support…ability for differentiation and functional integration into the host [heart] tissue” [8]. Tissue engineers are working towards finding a specific cell type that always differentiates into cardiac cells regardless of other variables. “It is important for the cell type of interest to differentiate into functional, force-generating myocardial [heart] tissue” [8]. To be successful, the stem cells will have to “increase in the muscle mass required to generate sufficient mechanical work to maintain the demands for blood flow” [8]. Once fulfilled, the stem cell is able to act as a heart cell, and in turn, help the heart return closer to its healthiest state.

RESULTS OF INNOVATION

Dr. Joshua Hare, a scientist on the board of Stem Cell Therapeutics, a Canadian company, says, “The totality of evidence from the clinical trials is positive…The heart is pumping more blood per beat” [1]. There is great optimism that this innovation will prevent heart failure in patients that have experienced a myocardial infarction (heart attack). Dr. Gustav Steinhoff from the Biomedical Research Center Rostock compiled a meta-analysis from the landmark trials over the last three years; the clinical studies in the compilation resulted in “an increase in ejection fraction (a measure used for how well the heart pumps blood) by 3% to 36% (mean 11.4%) and decreased infarct (the area damaged by the heart attack) size by 1% to 60% (mean 34%) when stem cell transplantation was executed eight to fourteen days after [the heart attack]” [5]. The wide range in values is primarily due to the different methodology of cell delivery, various ages of patients, and the amount of delivered cells. The important point to notice is that the statistics have always shown improvement (when the percentage is greater than zero) to the heart.

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FIGURE 1 [5]

Effect of Bone Marrow Stem Cell (BMC) Therapy on Survival

As seen in Figure 1, “there was an 11% decrease in long-term mortality over five years for treated patients in comparison to the control group” [5]. Engineers are searching for methods that will ensure higher percentages of ejection rate and infarct reduction for each and every patient receiving stem cell transplantation. The largest study in this field, STAR (acute and long-term effects of intracoronary Stem cell Transplantation in 191 patients with chronic heARt failure), included 391 patients with chronic heart failure led to similar statistics on the success of stem cell therapy where there was a 4% decrease in mortality for the stem cell group [5]. In all the studies done over the last decade as compiled by Dr. Steinhoff and STAR, there has always been an improvement in receiving stem cell therapy.

CONCLUSION: THE IMPACT OF THIS INNOVATION

“Each year, close to one million people in the United States have heart attacks” [1]. The ones who survive have to live the rest of their lives with a damaged heart. Heart attacks are a major contributor to heart failure, along with high blood pressure and diabetes [9]. The heart becomes weak and many of the cells in the heart become heavily damaged. “About five million people in the United States have heart failure” [9]. To once again emphasize, there is no cure for heart failure. The only treatment that exists for heart failure are “medicines and lifestyle changes [that] can help people who have the condition live longer” [9]. I want to be a force in this field so I can help make sure that someone else’s loved one does not have to die after a heart attack without a fight. I cannot stand such a prevalent issue in our society that is affecting millions, and yet there is no cure; there is just treatment that prolongs the patient’s life.

Stem cell therapy is an up and coming solution to preventing heart failure, yet has not gained traction worldwide. All of the studies conducted showed stem cells causing heart function improvement. “After years of seeing progress in heart failure treatment move forward incrementally, the prospect of cardiac regeneration [through stem cell therapy] has energized the field, opening up a new frontier for patients who otherwise have had no chance for recovery” [1]. As a future biomedical engineer, I want to work on improving stem cell therapy for treating patients by researching and testing out new methods. Engineers everywhere should be aware of this innovation that can save millions of Americans’ lives every year. Progress needs to be made in this area as quickly as possible, because there are many people dying every day due to heart failure. Many victims could have avoided their fate with stem cell therapy. Dr. Hare says, “Half of the [five million Americans currently experiencing heart failure] are going to die while we sort out our scientific understanding” [1]. I view engineering as a discipline that fixes problems; one of the biggest problems now in the world is the millions dying from something that does not have a cure. Heart disease is the number one cause of death in America, and it could be avoided with more research and experimentation, eventually making stem cell therapy the standard treatment patients receive. Stem cell therapy has the potential to be the treatment that can prevent heart failure.

REFERENCES

[1] L. Beil. (2011, October 22). “Reviving a tired heart: With a bit of encouragement, the life-giving muscle may renew itself.” Science News. (Online article). http://www.jstor.org/stable/41332724. pp. 26-29

[2] CDC. (2015). “Heart disease.” Center of Disease Control. (Online report). http://www.cdc.gov/heartdisease/facts.htm

[3] Harvard. (2012, December). “Stem cell therapy for heart disease.” Harvard Heart Letter. (Online article). p. 3

[4] NIH. (2015, March 5). “Stem Cell Information.” National Heart, Lung, and Blood Institute. (Website). http://stemcells.nih.gov/info/basics/pages/basics1.aspx

[5] B. Strauer, G. Steinhoff. (2011, September 6). “10 Years of Intracoronary and Intramyocardial Bone Marrow Stem Cell Therapy of the Heart: From the Methodological Origin to Clinical Practice.” Journal of the American College of Cardiology. (Online article). DOI: 10.1016/j.jacc.2011.06.016. pp. 1095-1104

[6] G.S. Cho, L. Fernandez, C. Kwon. (2014, September 22). “Regenerative Medicine for the Heart: Perspectives on Stem-Cell Therapy.” Antioxid Redox Signal. (Online article). http://www.ncbi.nlm.nih.gov/pubmed/25133793 pp. 2018-2031

[7] M. Gnecchi, Z. Zhang, A. Ni, V.J. Dzau. (2008, November 21). “Paracrine mechanisms in adult stem cell signaling and therapy.” PubMed Central. (Online article). DOI: 10.1161/CIRCRESAHA.108.176826. pp. 1-19

[8] K.R. Chien, I.J. Domian, K.K. Parker. (2008, December 5). “Cardiogenesis and the Complex Biology of Regenerative Cardiovascular Medicine.” Science Mag. (Online article). DOI: 10.1126/science.1163267. pp. 1494-1497

[9] NIH. (2014, March 27). “Explore Heart Failure.” National Heart, Lung, and Blood Institute. (Online website). http://www.nhlbi.nih.gov/health/health-topics/topics/hf

Acknowledgments

I would like to thank Mr. Chris Foley, my AP Biology teacher at Issaquah High School, WA for helping me have a solid foundation in biology. I would also like to thank Mr. Dan McMillan for helping me start off the paper with his presentation in my freshman engineering class. I would lastly like to thank Ms. Laura Waxman, a writing consultant at the University of Pittsburgh Writing Center, for solidifying this paper and fixing problems throughout it.