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Biomedical Engineering


Brenda Ogle and Nicholas Kouris

Assistant Professor Brenda Ogle with PhD student Nicholas Kouris (large image)

Fused cells promising for tissue regeneration

Tapping a leukemia virus for both inspiration and function, Assistant Professor Brenda Ogle and her collaborators are studying the biological effects of fusing adult stem cells with cardiac muscle cells, or cardiomyocytes. With funding from the National Institutes of Health, the researchers hope to learn more about cell fusion processes and, ultimately, to use that knowledge to develop therapies for heart attack patients.

During a heart attack, cardiomyocytes die. Afterward, the body replaces those cardiac muscle cells with fibroblasts, cells that form scar tissue instead of muscle tissue. At best, says Ogle, the heart pumps inefficiently; at worst, it fails completely. Fused with cardiomyocytes, stem cells could help restore lost heart muscle function.

Researchers generally acknowledge that cell fusion happens, yet they have just begun to study the mechanisms through which stem cells fuse with mature cells, and how, genetically, they form a single, functional cell.

Viruses are “experts” at fusing with other cells. Ogle’s collaborators include virologists Yoshihiro Kawaoka, a professor of pathobiological sciences, and Stacey Schultz-Cherry, a visiting associate professor of medical microbiology, both of whom have extensively studied virus fusion proteins. Already, the researchers have shown that by adding a viral fusion protein to the stem cell, they can dramatically increase the incidence of fusion between stem cells and cardiomyocytes.

Now, looking at both cardiac and stem cell microenvironments, they are studying the fused cells’ phenotype, or observable characteristics. Drawing on Cardiology Professor Timothy Kamp’s expertise in cardiac electrophysiology, the group will examine the cells’ mechanical and electrical function, as well as their ability to proliferate. Finally, the researchers will induce an artificial infarction, or heart attack, in animals and inject stem cells expressing the fusion protein into the affected region to investigate how the cells engraft and to study their phenotype and function. Throughout the research, the team also will monitor the fused cells for uncontrolled proliferation. “If there is a way of controlling cell fusion, and if cell fusion is biologically relevant in a beneficial way, then it will have implications for tissue regeneration beyond myocardial infarction,” says Ogle.

Biomedical engineers, clinicians collaborate on translational research

The W.H. Coulter Translational Research Partnership in Biomedical Engineering oversight committee has selected its fourth round of proposals for funding:

  • Targeted, accelerated MR spectroscopic imaging for treatment planning to maximize neural function in stroke patients (Medical Physics, Radiology & Biomedical Engineering Associate Professor Sean Fain; Radiology Researcher Krishna Kurpad, with Josh Medow of neurosurgery)

  • HYPRFLOW magnetic resonance angiography (Medical Physics, Radiology and Biomedical Engineering Professor Charles Mistretta; Radiology, Neurology and Neurological Surgery Professor Patrick Turski; Biomedical Engineering, Radiology and Medical Physics Associate Professor Walter Block; and Medical Physics Assistant Scientist Yijing Wu)

  • Nonlinear optical histopathology for clinical use (Biomedical Engineering and Clinical Pharmacology Associate Professor Patricia Keely, Pathology and Laboratory Medicine Professor Andreas Friedl, Professor David Beebe, with Kevin Elicieri)
  • Clinical assays for circulating tumor cell analysis (David Beebe, Medicine Associate Professor Doug McNeel, Medicine Assistant Professor Amye Tevaarwerk, with Mark Burkhard and Gleen Liu)

  • Orthopedic implant surfaces for enhanced healing (Assistant Professor William Murphy, Orthopedics and Rehabilitation Associate Professors Richard Illgen and Ben Graf and Assistant Professor Matthew Squire, and Orthopedics and Rehabilitation and Veterinary Medicine Professor Mark Markel)

  • A closed loop neural activity triggered stroke rehabilitation device (Assistant Professor Justin Williams, Radiology and Neurology Assistant Professor Vivek Prabhakaran, Senior Lecturer and Researcher Mitch Tyler, Neurology Assistant Professor Justin Sattin, with Dorothy Edwards)

  • Development of a biomimetic microlens array for improved medical imaging in laparoscopy and endoscopy (Electrical and Computer Engineering and Biomedical Engineering Associate Professor Hongrui Jiang, Surgery Associate Professors Jon Gould and Charles Heise, and postgrad trainee Carter Smith)

The Coulter Translational Research Partnership in Biomedical Engineering fosters early-stage collaborations between UW-Madison biomedical engineering researchers and practicing physicians. The collaborations will enable researchers to deliver advances more quickly to patients. The Biomedical Engineering Center for Translational Research promotes and facilitates these collaborative efforts.

The center develops partnerships, cultivates new translational research projects based on clinical practice needs, identifies and supports promising biomedical engineering collaborative research projects, and rapidly translates solutions into the clinic by fully using UW-Madison campus resources for technology transfer and commercialization.

Diseased tissue could provide clues to heart valve health

Popular worldwide for their cholesterol-lowering effects, statin drugs also show promise for treating or preventing heart-valve disease. Yet, prominent recent research both supports and refutes that claim. “Right now, it’s an area of great debate about statins and heart valves,” says Assistant Professor Kristyn Masters. “Do they stop the progression of heart valve disease or not?”

Masters, Mechanical Engineering Assistant Professor Kevin Turner, University of Pittsburgh Biomedical Engineering Professor Michael Sacks and their graduate students received nearly $1.7 million from the National Institutes of Health National Heart, Lung and Blood Institute to study tissue disease processes. They are designing diseased heart-valve tissue in the lab and plan to use the tissue as a platform to learn whether they can prevent heart valve disease, stop its progression, or cure it.

Statins figure heavily into their research. Initially, the group created two-dimensional diseased tissue models. The researchers treated the cell cultures with agents that increase calcification in the models, and with statins they showed disease inhibition and even regression. “On a molecular level, we’re understanding a lot more about what’s happening to these cells as they’re becoming more calcified,” says Masters.

Based on their newfound knowledge of cell-signaling mechanisms, the researchers also identified other agents that, in theory, also could prevent, stop or slow heart valve calcification. “This may lead us toward potentially identifying other drug classes that may or may not exist right now,” says Masters.

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