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Cardiovascular Stem Cell Working Group

This Working Group explores novel activities of stem cells which will be exploited to develop effective, safe, and durable therapies for cardiac and vascular diseases. The group has a range of investigators, including basic scientists and physician scientists, many of whom collaborate in teams to efficiently address important translational problems. The teams exploit cellular, tissues, and small animal and large animal models to study human cardiovascular disease. The work of one investigator, Dr. Kaushal, has led to a soon-to-open clinical trial with stem cells to be transferred into children with hypoplastic left heart syndrome.

Group Leader:

  • Terry Rogers, Ph.D.   

    The Rogers group has collaborated with Dr. Lederer to examine molecular and cellular actions of human bone marrow-derived mesenchymal stem cells (currently given to patients in clinical trials) on heart myocyte repair. These studies are being extended to exploit the inherent genetic diversity of clinically relevant mesenchymal stem cells with potentially greater plasticity, such as mesenchymal stem cells derived from adipose or placental tissues. These results will contribute to the development of allogeneic “off-the-shelf” stem cell therapies to replace myocytes which are now irretrievably lost from acute ischemia, chronic stress from disease, or aging.

    Rogers TB, Pati S, Gaa S, Riley D, Khakoo AY, Patel S, Wardlow RD, Frederick CA, Hall G, He LP and Lederer WJ. Mesenchymal stem cells stimulate protective genetic reprogramming of injured cardiac ventricular myocytes. J Mol Cell Cardiol 50, 346-356(2010).  

    Matthew Trudeau, Ph.D.  

    The Trudeau lab has used human induced pluripotent stem cell-derived cardiomyocytes to investigate defects in cardiac ion channels and their roles in cardiac arrhythmias and sudden death. The Trudeau lab exploits this stem cell-derived cardiomyocyte “disease-in-a-dish” model system to study the roles of specific ion channel genes, regulatory proteins, and disease mutants on ionic currents and cellular action potentials from stem cell-derived cardiomyocytes.

Group Members:

  • Jim Du, Ph.D.   

    The Du group uses a zebrafish model to study heart cell regeneration. This team takes advantage of the unique characteristics of zebrafish heart regeneration, and the genetic tractability of zebrafish, to study the molecular and genetic regulation of heart development, cardiomyocyte differentiation and dedifferentiation during heart regeneration. The ultimate goal is to find cures for human heart disease by reprogramming human cardiomyocytes to mimic the regenerative signals seen in zebrafish cardiac myocytes.

  • Bartley Griffith, M.D.  

    Dr. Griffith, a cardiac surgeon leads a team that investigates treatments for infarcted hearts. Current work centers on directly injecting mesenchymal stem cells into regions adjacent to experimental cardiac infarcts in large animal models. His team has shown that injected mesenchymal stem cells resulted in improved recovery of the heart in the area neighboring the infarct, and multiple measured cardiac functional parameters were improved, including contractile strain, cardiomyocyte apoptosis, incidence of fibrosis, and calcium handling.

    Zhao et al. (2012). “Mesenchymal Stem Cell Transplantation Improves Regional Cardiac Remodeling Following Ovine Infarction”. Stem Cells Translational Medicine 1:685-695. 

  • Sunjay Kaushal, M.D., Ph.D.  

    Dr. Kaushal, a pediatric cardiac surgeon, identified relatively abundant endogenous cardiac stem cells in the right atrial appendages (removed as standard procedure during many pediatric reconstructive cardiac surgeries) of infants with congenital heart disease. He has expanded these cells in the lab and has shown that they possess remarkable regenerative capacity when transferred into damaged rodent hearts. The team has obtained FDA approval to ex vivo expand and transplant these cardiac stem cells back into autologous congenital heart disease patients, in a first-in-children clinical trial to be conducted in University of Maryland and Johns Hopkins patients designed to demonstrate safety and efficacy in delaying the need for successive surgeries for hypoplastic left heart syndrome.

    Simpson DL, Mishra R, Sharma S, Goh SK, Deshmukh S, Kaushal S. “A strong regenerative ability of cardiac stem cells derived from neonatal hearts.” Circulation. 2012 126 (11 Suppl 1):S46-53 

  • W. Jonathan Lederer, M.D., Ph.D.  

    The Lederer team has shown that mesenchymal stem cells isolated from adult human bone marrow (currently being given to patients post-myocardial infarction in clinical trials of Osiris, a Maryland company) can protect cardiac myocytes from stress and restore normal intracellular calcium signaling function to damaged cardiac myocytes. These direct beneficial effects are mediated though a paracrine signaling cascade that includes genetic reprogramming of the cardiac myocytes themselves.

    Rogers TB, Pati S, Gaa S, Riley D, Khakoo AY, Patel S, Wardlow RD, Frederick CA, Hall G, He LP and Lederer WJ. Mesenchymal stem cells stimulate protective genetic reprogramming of injured cardiac ventricular myocytes. J Mol Cell Cardiol 50, 346-356(2010)  

  • Anthony Passaniti, Ph.D.  

    TThe Passaniti team is studying angiogenic strategies mediated by mature resident human endothelial cells (ECs) in injured tissue and their ability to re-express stem cell markers during vessel expansion, which are important in blood vessel reconstitution and wound healing. They are identifying transcription factors that promote vascular EC proliferation, cell cycle progression, migration, and survival, thus stimulating neovascularization. This could lead to the development of a panel of human tissue-specific ECs for regeneration or transplantation in a variety of clinical settings that recruit ECs including corneal repair, coronary artery bypass, retinal healing, neural regeneration, diabetic wounds, and repair after traumatic injury (military).

  • Richard Pierson, M.D.   

    Dr. Pierson, a cardiac transplant surgeon, exploits primate models of cardiac transplant immunology to evaluate trafficking of injected stem cell populations, and to track cell fate (maturation, differentiation, etc.). The Pierson team is exploring the use of bone marrow stem cell transplantation for the facilitation of tolerance induction to protect heart allografts across a full major histocompatibility complex (MHC)-mismatched barrier in a primate (cynomolgus) model.

  • Mark Pittenger, Ph.D. 

    The Pittenger group is developing methods to improve the delivery, survival, and engraftment of mesenchymal stem cells in the damaged heart in small and large animal models, in collaboration with the Griffith team. The group is developing a “survival cocktail” that can be used to pre-treat stem cells before delivery in the clinic for better healing outcomes than are currently seen in heart infarction patients. The lab uses in vitro, small animal and large animal models.

    Zhao et al. (2012). “Mesenchymal Stem Cell Transplantation Improves Regional Cardiac Remodeling Following Ovine Infarction”. Stem Cells Translational Medicine 1:685-695.  

  • Rajabrata Sarkar, M.D., Ph.D.  
  • Mark Vesely, M.D.  

    Dr. Vesely, an interventional cardiologist, is leading the Division of Cardiology’s participation in two multi-centered clinical trials involving the delivery of adult stem cells to patients following acute myocardial infarction (MI). He is initiating additional observational studies to facilitate the development of a clinical trial focused on the chronic heart failure (HF) population. He is also collaborating with the Griffith, Pittenger and Kaushal teams to establish large animal models of acute MI and chronic HF. His specific interests include investigation of the timing and methods of delivery of stem cell therapies.