How do you mend a broken heart? When it comes to love, this is a difficult question to answer. However, when it comes to heart failure, a leading cause of death worldwide, scientists are finding that the answer might be found within the heart. In 2009, researchers discovered that the heart is able to generate heart cells throughout a person’s lifetime. CORRECTION: This finding means that developing new stem cell-based strategies to treat heart failure is now becoming a feasible option.
In this author spotlight, Georgina Ellison, a Reader at Liverpool John Moores University, answers a few questions about her team’s recently published article on how cardiac stem cells (CSCs) not only have the increased ability to replace lost heart muscle but also have a ‘paracrine’ effect on the survival of heart muscle cells.
During my PhD studies I discovered some small newly formed cardiomyocytes in the injured cardiac samples I was working on. Considering the accepted paradigm of the heart at that time was as a non-proliferative organ I did not think what I found was possible, therefore I contacted Professor Bernardo Nadal-Ginard, a world-leading expert in this field, and asked for his opinion on my findings. Prof. Nadal-Ginard was very interested in what I had discovered and offered me the opportunity to come and study further in his lab in New York, using state of the art techniques and technologies and work with his team of first class experienced researchers.
In the paper you mention that there have been many types of stem cells suggested as suitable candidates for heart cell regeneration. Bone marrow derived cells (BMDCs) are one of these suggested candidates however, you suggest using cardiac stem cells instead. Can you explain why CSCs seem to be more promising?
So far clinical trials have used bone marrow derived cells (BMDCs) for heart repair after a heart attack. However, the improvements in heart function are modest and this could be because the bone marrow cells are not the best type of cell to be used to regenerate the lost contractile heart muscle or cardiomyocytes. We show that the endogenous CSCs have potent cardiomyocyte regenerative potential and also play a paracrine role by improving cardiomyocyte survival. In the new era of regenerative medicine it is essential to ascertain the ‘optimal’ type of cell to be used for regenerative myocardial therapies and a cell that has regenerative and renewal capacity, as well as exerting pro-survival and paracrine effects would be the ideal cell of choice.
Of the videos in your manuscript, you highlighted the one above as particularly interesting. The cells in the video express high levels of GATA-4, which is an important early maker gene in cardiomyocyte development. Can you explain why this video is notable?
This video shows that even when the GATA-4 highly expressing CSCs do not have direct cell-to-cell contact with the cardiomyocytes, the cardiomyocytes’ contractility is maintained for up to 3 weeks in vitro. This has never been shown before and was not apparent when other types of cells were used, i.e. fibroblasts or GATA-4 low expressing CSCs.
What is your next big research project? Or where do you want to go from here?
Our next big research project is to establish and manufacture the optimal cardiac regenerative treatment and this regenerative therapy must be an off-the-shelf, safe, effective, simple, available to all and affordable treatment.
Why did you decide to publish in PLoS ONE?
Because it is open access and freely available online, which is how it should be nowadays. Also, it has added features such as being able to comment on papers and metrics information on papers. Altogether, these contribute greatly to the overall impact of your research, and assessing impact is now very important in biomedical research.
The paper by Ellison, Nanako Kawaguchi, Andrew J. Smith, Cheryl D. Waring, Md Kamrul Hasan, Shinka Miyamoto and Rumiko Matsuoka paper is entitled, c-kitpos GATA-4 High Rat Cardiac Stem Cells Foster Adult Cardiomyocyte Survival through IGF-1 Paracrine Signalling. This paper is freely available to comment on, read and rate. If you are interested in reading more about stem cell therapy research you can try searching here.
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