Stem cells spark new avenues for heart research
The jointly run Institute of Biosciences and Medical Technology (BioMediTech) provides a framework for closer formal and informal collaboration between scientists from Tampere University of Technology and the University of Tampere, such as Katriina Aalto-Setälä and Esa Räsänen.
A chance encounter between researcher and cardiologist Katriina Aalto-Setälä and physicist Esa Räsänen led to a project that looks beyond the conventional wisdom on cardiovascular health.
Aalto-Setälä and Räsänen met in December 2012 at a public lecture showcasing the achievements of newly crowned Nobel laureates. Both had been asked to reflect on the achievements of Nobelists in their own fields of research.
Professor Katriina Aalto-Setälä leads the Heart Group based in the Institute for Biomedical Technology at the University of Tampere. The speech she gave at the event covered the seminal work of Shinya Yamanaka, who found a way to reprogramme mature cells to become pluripotent stem cells that are capable of differentiating into virtually any cell type in the human body, such as heart cells or neurons. The discovery of these so-called induced pluripotent stem cells, or iPS cells, stunned the scientific world and earned Yamanaka the joint Nobel Prize in Physiology or Medicine in 2012.
Aalto-Setälä was delighted to introduce the audience to iPS research. She worked with Yamanaka at the Gladstone Institute in San Francisco right after he had published the results that led him to receive the Nobel Prize. She studied the process of transforming iPS cells into heart cells and brought her new-found expertise to Tampere upon her return.
”I had travelled to the USA in search of new ideas and got to witness a sensational discovery in the making,” recalls Aalto-Setälä.
WHO? Associate Professor Esa Räsänen
- Master’s degree in theoretical physics from the University of Helsinki in 2001, doctorate from Helsinki University of Technology in 2004. Has worked as a researcher in Berlin for three years and spent shorter stints in Linz and Harvard. Joined the University of Jyväskylä as an academy research fellow in 2008.
- Head of the Quantum Control and Dynamics Group in the Department of Physics at Tampere University of Technology.
- Was appointed to a tenure track position at TUT in autumn 2012. The tenure track system offers researchers a clearly defined career path towards a full professorship.
Time series analysis from a new angle
In addition to citing Yamanaka’s achievements, Aalto-Setälä touched on her own research into reprogrammed stem cells, catching the immediate attention of Esa Räsänen who was sitting among the audience.
“I’m a theoretical physicist who specializes in computational methods, and my primary research interests have nothing to do with medicine, biology or even biophysics. Katriina’s speech got me thinking about heart cells beating in a petri dish. I started to wonder whether time series analysis could be applied to rhythmically contracting cells,” says Associate Professor Esa Räsänen from the Department of Physics at TUT.
Räsänen was introduced to the concept of time series analysis while working as a researcher at Harvard University a couple of years ago. He has used the method to analyse music at TUT.
“When applied to music, the main purpose of time series analysis is to identify the presence of fractal properties, meaning that the human deviations from a “perfect” rhythmic timing obey a complex pattern that repeats itself across different scales.”
“Fractal properties can also be observed in our heart rate. It may seem counterintuitive, but the variability underlying beat-to-beat intervals is not random“, explains Räsänen.
Direct benefits to patients
WHO? Professor Katriina Aalto-Setälä
- MD in 1986, PhD in 1989, Adjunct Professor in 1995, Specialist in Internal Medicine in 1999, Specialist in Cardiology in 2002 and currently Professor of Cardiology.
- Postdoc fellow at The Rockefeller University from 1990 to 1993, St. Jude Children’s Research Hospital from 1993 to 1994, visiting professor at the Gladstone Institute from 2007 to 2008,
The off-duty collaboration between Aalto-Setälä and Räsänen is driven by sheer scientific curiosity. It is early days yet, but they are planning to create models of the active behaviour of both healthy and unhealthy cardiac muscle cells and find out what abnormalities look like at the cellular level.
According to Räsänen, previous research suggests that fractal analysis of the human heartbeat can provide important insights into cardiovascular health.
“A decrease in the fractal dimension of the heartbeat is a normal part of the ageing process, but it can also be a sign of illness,” he says.
Katriina Aalto-Setälä, who works both as a researcher at the University of Tampere and as a cardiologist at Tampere University Hospital, expects the research efforts to directly benefit people living with heart disease.
“Modern medicine has had relatively little to offer to heart patients. The human heart is a complex organ and many of its diseases, such as cardiomyopathy, are caused by multiple genetic abnormalities. It’ll be interesting to see whether Esa and I find new patterns that indicate an increased risk of heart disease and sudden death,” she says.
“The application of fractal analysis to cardiovascular health opens up fascinating and previously unexplored avenues of research”, adds Räsänen.
ECG data analysed at TUT
The process of generating iPS-derived heart cells begins with Katriina Aalto-Setälä taking a biopsy of a person’s skin, usually from the lower back. After the skin cells are bathed in the right cocktail of nutrients and left to grow for a few weeks, they transform into pluripotent stem cells that Aalto-Setälä can differentiate into specialized heart cells.
The in vitro culture of heart cells is placed on top of ECG electrodes that measure the electrical activity of the cells. This is the data that is analysed by Esa Räsänen and his research group.
Aalto-Setälä says that Yamanaka’s approach has had a profound effect on stem cell research, as it avoids the ethically contentious step of harvesting stem cells from human embryos that are left over from fertility treatments. In addition to ethical considerations, embryonic stem cells tend to show a high degree of variability.
“Most importantly, iPS cells are a genetic match to the donor and therefore allow scientists to analyse the genetic defect associated with the donor’s condition,” emphasizes Aalto-Setälä.