CT Surgery Research Lab

Research Director: J. Yasha Kresh, Ph.D.

Learning and scholarly interaction are fostered in an atmosphere of discovery within the Cardiothoracic Research and Cardiovascular Biophysics Laboratory, which is an interdisciplinary core facility bridging the Department of Cardiothoracic Surgery and the Division of Cardiovascular Diseases. The research projects draw on a large multidisciplinary knowledge base, applying the thinking, phenomena, techniques, and technology of cardiovascular engineering, cellular and tissue engineering, biophysics, mathematical/computational biology and systems theory to the solution of basic and clinical cardiovascular problems. The broad range of research projects that been pursued reflects this unique interdisciplinary approach. Importantly, this facility also serves as an educational cardiac research center to direct the scientific projects of medical and surgical residents, as well as graduate and medical students. In addition, the collaborative efforts include projects with the Tissue Engineering and Robotic Surgery groups at Drexel University

The CT-Surgery Lab is a multi-disciplinary research facility, currently supporting the activity of two Bio-engineering graduate students and one Post Doctoral Surgical Research Fellow.

Our research portfolio consists of:  

1.  A comprehensive program focused on the surgical management of end stage heart failure

This overarching effort includes investigation of:

• Topobiology of cellular cardiomyoplasty (milieu-dependent cardiomyocyte differentiation and adaptation)
• In vitro "pre-programming" of adult stem cells (hMSC commitment, differentiation)
• Molecular imaging and assessment of remodeled human hearts (role of MMP-3 and TIMP-1)
• Effects of temporary ventricular support devices on cellular and biochemical markers of left ventricular reverse-remodeling
• Long-term cardiac and pulmonary functional substitution with artificial devices and electrically active polymer muscle constructs.

2. Efforts to improve the capabilities of robot-assisted cardiac surgery, through the incorporation of sensors that provide haptic (tactile) feedback to the user, and through improvements in computer imaging and vision.

3. Tele-linked collaborative research programs focused on cellular interactions using a unique, custom-designed live-cell observatory. This allows multiple researchers to view and interact with cell cultures from remote distances in real time.

Topobiology of  Cellular Cardiomyoplasty

Our work is focused on cell based therapy for heart failure. The goal is to utilize autologous human stem (adult stromal bone marrow, i.e., mesenchymal) cells (hMSC) for the repair and /or regeneration of the damaged cardiac tissue.

In particular, understanding the microenvironment-dependent (target niche) signals  that can induce transdifferentiation of hMSC to cardiac phenotype is of paramount importance. The Microarray-based gene expression profiling technology will enable us to identify the key (network of) genes that are activated by the various ex-vivo imposed (culture) conditions (ex. growth factors, ECM, mechanical/electrical "preconditioning"). Understanding the conditions /cues involved in controlling the plasticity of hMSC is a prerequisite for engineering functional (and large scale) cardiac tissue integration.

Homing Stem Cells for Cardiac Repair

When a blockage of the coronary artery occurs, cardiomyocytes become injured. This injury induces the release a variety of cytokines as well as chemokines into the circulation. Chemokines play a pivotal role in "pulling" endothelial progenitor cells from the bone marrow and directing them to areas of injury. We hypothesize that the injured cardiac cells serve as the signaling nidus, initiating the chemokine mediated chemotactic gradient; acting as a local homing signal directing these stem cells towards the infracted area.

The experimental protocols are designed to establish the presence and quantify the cytokines/chemokines in peripheral circulation in response to myocardial injury, and evaluate the corresponding numbers of stem cell in circulation. This information will benefit the growing field of cell-based therapy that is attempting to repair and restore the injured myocardium. This may provide a means by which autologus progenitor cells can be chemically guided to both prevent the progression of myocyte injury following infarction, as well as, a potential therapy for treating end stage heart failure. The identification and quantification of both cytokines and chemokines, may aid in the development of a new marker for myocyte injury, leading to new screening tools for the early diagnosis of myocardial infarction. In addition the knowledge gained by understanding the process by which endogenous stem cells home to an area of injury will allow for the development of new therapies for guiding the healing process not only in the heart, but in other organ systems as well.