Stem Cells & The Heart

Towards Safe and Effective Stem Cell Therapies

Every day, billions of cells die in the human body and are replaced by new ones. This shows the remarkable ability of many human organs to regenerate and heal after damage. However, this is not always the case; our heart consists of muscle cells called cardiomyocytes, which are fundamental for making our heart beat. When those cells die, either due to chronic disease or a heart attack, they cannot be regenerated. This is where novel therapies involving human stem cells come into play. “Replacing dead cells with transplants may contribute to heart function”, says Chunhui Xu, Ph.D., an Associate Professor of Pediatrics at Emory University School of Medicine and Director of the Cardiomyocyte Stem Cell Laboratory at the Department of Pediatrics. “Dr. Xu is, without any doubt, a world-renowned expert in stem cells”, says Sean Kim, the case manager working with Xu at the Office of Technology Transfer.

Chunhui Xu
Chunhui Xu

Human pluripotent stem cells have the ability to become any type of specialized cell in the human body – muscle, heart, liver, pancreas, etc. Usually, these cells can be found in the embryonic stage, and are very rare in adults. For a long time, this was an unsolvable problem for scientists. However, in the past years, researchers have come up with a solution to that issue: Induced Pluripotent Stem Cells, or iPSCs, are adult cells reprogrammed to reverse to the embryonic state, which means they can again become any type of tissue we want, if we provide them with the right environment.

Xu and her team are dedicated to advancing stem cell technology and therapies, with a special focus on the human heart. Her lab has multiple ongoing projects that will advance the transition “from stem cell to heart cell.” For example, they are using stem cells for disease monitoring and studying potential drug responses. When scientists use iPSCs derived from the tissue of a specific patient – usually from the skin or blood – they can work with the patient’s specific genetic information and study the disease phenotype on a Petri dish. Xu gave the example of a patient at Children’s Hospital who had a rare genetic mutation causing arrhythmia that did not respond to beta blockers, the most common arrhythmia medication. Using patient derived iPSCs, they found a better drug that fixed the arrhythmia in iPSC-derived cardiomyocytes. “We then saw that the same drug that inhibited arrhythmia in the dish worked well on the patient”, says Xu.

However, when thinking about stem cell use for transplantation, safety is paramount. As Xu explained, when iPSC-derived differentiated cells are transplanted to a patient, any residual stem cells left in the final cell product can cause tumors. To solve this problem, Xu collaborated with biomedical engineers at Georgia Tech to develop a sensitive assay that uses nanotechnology to detect even the smallest amount of residual stem cells, leading to a better, safer end product. The surface-enhanced Raman scattering (SERS)-based assay, as this method is called, exceeds all previous methods in terms of sensitivity. In fact, it is able to detect even one residual stem cell among a million cells. This holds promise for efficient quality control of future stem cell applications and may accelerate the process through which stem cell research eventually reaches the clinic. Furthermore, another collaboration with a Georgia Tech lab yielded a new technology for eliminating residual stem cells using virus-like particles that specifically target and kill stem cells. This way, the end product can be completely safe for clinical applications.

Residual stem cell detection using nanotechnology assay. Han et al., Biomaterials. 105:66-76 (2016)
Process Graphic

Another important component of developing stem cell-derived transplants is finding the right setting and environment that promotes differentiation of stem cells into adult cardiomyocytes. For that purpose, Xu and her team are sending their cells to space! It turns out that zero-gravity conditions allow progenitor cells, which are the precursors to cardiomyocytes, to grow faster and produce cardiomyocytes at a larger quantity and higher purity. Through their collaboration with NASA, they are studying how space affects stem cell differentiation and are hoping to achieve similar conditions in the lab.

In the future, Xu hopes to continue pushing the boundaries of stem cell research. “My main goal right now is to push cells into a more mature stage that is even closer to the human condition” says Xu, a development which will bring her discoveries even closer to the clinic. She is also interested in studying different types of cardiotoxicity using stem cells, something which will help us understand why heart cells die in response to certain medications. Overall, Xu and her team are excited about the opportunities that will arise using their technologies and discoveries. So is Sean Kim, who is confident that her open-mindedness and expertise in science will overcome one of the greatest challenges in developing effective therapies against cardiovascular diseases.

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