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Professor, BIO5 Institute
Professor, Medicine - (Research Scholar Track)
Our lab has a new treatment for heart failure. We have a biodegradable graft seeded with adult human cells that we put on the surface of the heart. The potential is to regenerate new heart muscle
Research in my laboratory over the last 30 years has focused on chronic heart failure (CHF), its pathophysiology and the development of new treatments for CHF. We have developed clinically relevant animal models of heart failure that allow us to explore the translational potential of new treatments. Our work initially examined the role of afterload reduction and neurohormal blockade. More recently we have been working with cell-based therapy for CHF using bioengineered scaffolds to prevent left ventricular (LV) remodeling and restore function in the damaged heart. Our most effective scaffold is a biodegradable vicryl mesh with embedded viable neonatal fibroblasts that secrete angiogenic growth factors. This patch increases myocardial blood flow, improves LV systolic function, and reverses LV remodeling if implanted at the time of an acute myocardial infarction. In CHF, this patch still improves myocardial blood flow but does not improve LV function or reverse LV remodeling. Thus, we have an effective delivery system for cell based therapy for CHF that increases myocardial blood flow and provides structural support for new cell growth. We are now focusing on seeding this patch with human inducible pluripotent stem cells in the cardiac lineage, the seeded cardiomyocytes align, communicate, contract in a spontaneous and rhythmic fashion. When implanted in rats with CHF, they improve LV function. We are exploring this patch seeded with human inducible cardiac pluripotent stem cells to treat patients with CHF.
Keywords: induced pluripotent stem cells
Desai, A., Choi, B., Dudley, S. C., Kittles, R., Machado, R. F., Garcia, J. G., Hillery, C., Indik, J. H., Goldman, S., Juneman, E. B., Groth, J., Nair, N., Rutledge, C., Kanady, J., Fleming, I., Batai, K., Weigand, K., Shi, G., Kim, T. Y., , Gupta, G., et al. (2018). IL-18 is a novel mediator of prolonged QTc and ventricular arrhythmias associated with Sickle Cell Disease. Proceedings of the National Academy of Sciences.
Joe GN Garcia, Steven Goldman
Holman, W. L., Davies, J. E., Lin, J. Y., Wang, Y., Goldman, S., Bakaeen, F. G., Kelly, R., Fremes, S. E., Lee, K. K., Wagner, T. H., Sethi, G. K., & , V. C. (2013). Consequences of radial artery harvest: results of a prospective, randomized, multicenter trial. JAMA surgery, 148(11), 1020-3.
To date, no study has defined the consequences of radial artery harvest based on a large number of patients in a prospective randomized trial.
Lancaster, J., Juneman, E. B., Sanchez, P., Weigand, K., Moukabary, T., LaHood, N., Pandey, A., Chinyere, I. R., Stansifer, M., Daugherty, S., Bahl, J. J., & Goldman, S. (2016). Human Induced Pluripotent Stem Cell Derived Cardiomyocyte Tissue Engineered Patch Improves Left Ventricular Systolic/Diastolic Function and Electro-Mechanical Coupling in Rats with Heart Failure. Circulation Research, 119(Supl 1), A360.
Sanchez, P., Lancaster, J. J., Weigand, K., Mohran, S. E., Goldman, S., & Juneman, E. (2017). Doppler Assessment of Diastolic Function Reflect the Severity of Injury in Rats With Chronic Heart Failure. Journal of cardiac failure, 23(10), 753-761.
For chronic heart failure (CHF), more emphasis has been placed on evaluation of systolic as opposed to diastolic function. Within the study of diastology, measurements of left ventricular (LV) longitudinal myocardial relaxation have the most validation. Anterior wall radial myocardial tissue relaxation velocities along with mitral valve inflow (MVI) patterns are applicable diastolic parameters in the differentiation between moderate and severe disease in the ischemic rat model of CHF. Myocardial tissue relaxation velocities correlate with traditional measurements of diastolic function (ie, hemodynamics, Tau, and diastolic pressure-volume relationships).
Pandey, A. C., Lancaster, J. J., Harris, D., Goldman, S., & Juneman, E. B. (2017). Cellular Therapeutics for Heart Failure: Focus on Mesenchymal Stem Cells. Stem Cell International, 2017, 12. doi:doi.org/10.1155/2017/9640108