About This ProjectEvery year, 55,000 deaths in the United States are caused by heart failure. Our lab studies genetic heart defects by reprogramming patient skin cells into stem cells that we then turn into heart cells. These heart cells are used to study each patient's specific genetic disease (focusing on CPVT, which causes arrhythmias and sudden death). With your help, we can move closer to curing our patients and others in danger from a genetic heart defect.
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What is the context of this research?
According to the Center for Disease
Control and Prevention, 25% of deaths in the United States are the result of heart disease. Of these, 55,000 are the victims of sudden death each year. Here at the C.A.R., we reprogram patient skin into human induced pluripotent stem cells (hiPSCs) and then push them to become heart cells. We then use these cells to study disease development, so that we can move closer towards both finding a cure and personalized regenerative therapy.
What is the significance of this project?
We've focused our resources on developing stem cells from patient samples taken from several family members with CPVT at the University of Michigan Hospital. These diseased cells carry within them the genetic code for the heart disease that we are hoping to understand, and will also allow us to tell the clinicians whether or not the newborn family member will be plagued by the same issues as the diseased parent and siblings.
We have been able to reprogram skin cells into stem cells. Now, we are in the process of turning those cells into heart cells that beat spontaneously and form mini heart-like organs. We then compare the differences between diseased and healthy heart cell development. This helps us target new areas for drug treatment and therapy.
What are the goals of the project?
Unfortunately, stem cells are very expensive to make and maintain, although they represent a limitless supply of resources for studying diseases if we have the proper supplies to keep reprogramming and growing them. In order to continue with our research, we need bioengineering supplies.
We've been able to successfully reprogram several patient's skin cells into stem cells. The next step is to continue turning the disease specific stem cells into heart cells and compare them to our healthy stem cell-derived heart cells. For this, we need transcription factors, media, nutrient supplements, and antibodies.
We also need materials to continue reprogramming the rest of the skin samples that we've already received from the family of patients. This will help us to continue studying CPVT and to discover whether the newest family member will need a defibrillator implanted for managing the arrhythmias caused by this disease.
The total budget for this project is $9,000.
We are in the process of reprogramming cells from patients diagnosed with CPVT. In order to continue our work, we need to have several cell lineages (one for each patient). That means that we need several round of materials to reprogram the skin cells into stem cells. These materials alone will cost $2,000 in order to reprogram all of the family's samples. Once we've reprogrammed a line, we also need to turn the new stem cells into heart cells. This will cost an additional $1,000 overall.
In order to compare the diseased lines with the healthy ones that we have already created, we use qRT-PCR, Western Blots, and immunohistology staining. All of these techniques require antibodies that are both heart specific and ones that are specific for the areas that we are targeting as specific for the disease, which will cost $2,000 altogether.
In order to make the cells necessary for our research, we need special media and nutrient supplements for each cell type. These expenses make up the bulk of our need currently, and will cost $4,000.
Meet the Team
Team BioI began working at the CAR as an undergraduate student volunteer. At that time, I started training in stem cell culture techniques. Now that I have my degree, I direct our reprogrammed stem cells into heart cells called myocytes. I also train new students to grow stem cells. These newly minted researchers help with several projects, including reprogramming our disease-specific cells. Your support is greatly appreciated by me, my colleagues, and our patients. With your help, I'll be able to continue making heart cells from both our healthy and diseased stem cells, so that we can compare their differences using a variety of methods. There's nothing more exciting that looking at a plate of what used to be stem cells and seeing the bottom of the plate beating when it wasn't the day before!
When I'm not working with stem cells, I enjoy a good laugh by re-watching episodes of the Big Bang Theory and snowmobiling in the Upper Peninsula with my family (we get a lot of snow here in Michigan!).
Press and MediaThe Center for Arrhythmia Research Official Website
Additional InformationRecent publications:
Myosin light chain 2-based selection of human iPSC-derived early ventricular cardiac myocytes Published in Stem Cell Research; 2013
Extracellular Matrix Promotes Highly Efficient Cardiac Differentiation of Human Pluripotent Stem Cells The Matrix Sandwich Method Published in Circulation Research; 2012
Simultaneous Voltage and Calcium Mapping of Genetically Purified Human Induced Pluripotent Stem Cell–Derived Cardiac Myocyte Monolayers Published in Circulation Research; 2012
Myofilament incorporation and contractile function after gene transfer of cardiac troponin I Ser43/45Ala Published in the Archives of Biochemistry and Biophysics; 2013
Inhibition of platelet-derived growth factor-AB signaling prevents electromechanical remodeling of adult atrial myocytes that contact myofibroblasts Published in Heart Rhythm; 2013
Optical Imaging of Voltage and Calcium in Cardiac Cells & Tissues Published in Circulation Research; 2012
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