The Medical College of Wisconsin (MCW) and Cellular Dynamics International (CDI) have announced receipt of a research grant award from the National Heart, Lung, and Blood Institute (NHLBI) to investigate the mechanisms underlying Left Ventricular Hypertrophy.
Commonly known as an increase of the size and weight of the heart, Left Ventricular Hypertrophy is a common and major risk factor for heart disease and heart failure due to high blood pressure or diabetes.
The MCW and CDI will use the grant funds, totalling $6,255,632 over 5 years, to generate 250 induced pluripotent stem cell (iPSC) lines from blood samples drawn from Caucasian and African-American families in the Hypertension Genetic Epidemiology Network (HyperGEN).
All of these families have an elevated burden of high blood pressure and are at significant risk for cardiovascular disease. The iPSC lines will then be differentiated into ventricular heart cells for use in experiments to better understand the genetic mechanisms underlying this disease.
iPSCs are created from adult cells, such as blood or skin, which are reverse engineered to a stem cell state, from which point they can turn into any cell type in the body. iPSCs can be made from any individual and avoid the political and ethical issues surrounding embryonic stem cells.
An increase of the weight of the heart is a common precursor of serious disorders including myocardial infarction and congestive heart failure. This grant will enable researchers to improve future methods for diagnosis, treatment, and prevention of these conditions.
HyperGEN involves scientists from six universities and the NHLBI who seek to identify the genetic contributions to hypertension. HyperGEN is unique because it is family-based, includes both Caucasians and African-Americans and is one of the largest genome-wide association studies (GWAS) with extensive clinical data available.
”This grant builds on years of our research to identify genes for this disease. We now have the wonderful opportunity to capitalize on the latest stem cell technology to study human heart cells in the laboratory,” said Ulrich Broeckel, MD, Professor of Pediatrics, Medicine and Physiology at MCW and Associate Director at the Children’s Research Institute.
Broeckel continued, “This technology is truly revolutionary since each cell line stands for an individual patient, and we can now start to study the unique disease mechanisms and test new treatments and drugs based on each individual’s unique genetic makeup. This grant also shows the strength of collaborations between academic investigators and a company which leads to cutting edge research.”
“Funding of this grant will enable Cellular Dynamics to generate an unprecedented 250 human iPSC lines as well as heart cells derived from those lines,” said Emile Nuwaysir, Chief Operating Officer of CDI.
Nuwaysir continued, “Until now, functional studies for left ventricular hypertrophy have been limited because human primary cardiomyocytes, or heart cells taken from living tissue, were not available for functional analysis. Human iPSC technology provides a solution to this problem. CDI’s human iPSC-derived heart cells, iCell® Cardiomyocytes, exhibit properties highly similar to human primary cells and thus are a relevant model system for the required functional analysis. In addition, CDI is the only company with the capability to manufacture iPSCs and differentiate them in large numbers and at high quality and purity from a typical, standard blood draw, thus enabling MCW to perform this series of experiments. We are particularly excited about this project because we see it as a harbinger of the next big scientific wave: the linking of genotype to phenotype through iPSC-derived terminal tissue cells.”