A novel "smart" materials framework that encourages adult stem cells in laboratory cultures to differentiate into heart cells will be presented at the American Society for Cell Biology (ASCB) 49th Annual Meeting, Dec. 5-9, 2009 in San Diego.
The University of California, San Diego (UCSD) scientists who conducted the research "grew" the stem cells on a hyaluronic acid (HA) framework that they engineered to chemically mimic the alterations in elasticity that normally occur in the protein scaffold that supports body cells.
More adult stem cells differentiated into heart muscle cells, or cardiomyocytes, on the HA framework than with conventional laboratory techniques, said the scientists, Jennifer L. Young and Adam J. Engler, Ph.D., of UCSD's Jacobs School of Engineering bioengineering program.
To engineer the "smart" framework, Young and Engler used atomic force microscopy (AFM) to measure the changes in elasticity that normally occur in the extracellular matrix (ECM), the 3-dimensional scaffolds of collagen, fibronectin and other materials that surround the body's adult cells and mold embryonic stem cells into functioning heart muscle cells
Guided by the elasticity measurements determined by AFM, the scientists finely-tuned their laboratory-produced matrix so it would polymerize over time, growing stiffer through cross-linking and squeezing stem cells in the way that the body's ECM normally shapes stem cells.
"By tuning this material to mimic in situ time-dependent stiffness changes, cells placed in this material indicate improved cardiac differentiation," said Young, adding that subsequent studies in animal models hopefully will hone the technique for possible therapeutic application to help regenerate healthy cardiac muscle and restore cardiac function to human patients' damaged hearts.
Such stem cell therapy would supplement the body's normal repair mechanisms. For example, when the heart muscle is damaged from a heart attack, the heart signals the bone marrow to release adult stem cells.
By replacing dead or impaired cells, these stem cells help the weakened heart muscle to regain its pumping power. However, since this self-repair process is short-term, the patient's heart tissue often remains partially damaged.
Young pointed out that other scientists have attempted, but failed, to treat patients with heart disease by injecting adult stem cells directly into their damaged heart muscle.
In these experimental therapies, called cellular cardiomyoplasty, the injected stem cells took their cues not from the elastic ECM, but from the patients' stiff, scarred cardiac muscle wall, Young explained and added that in these clinical trials, the patients' heart wall stiffness decreased only slightly, and their cardiac function marginally improved.
Heart disease is the leading cause of death in the U.S., killing 631,636 Americans in 2006, according to the U.S. Centers for Disease Control (CDC).
Jennifer L. Young (jly004@ucsd.edu; (858) 246-0332) will present poster, "Engineered 'Smart' Materials for Improved Cardiomyocyte Differentiation," on Tuesday, Dec. 8, during the 12:30-2:00 pm Poster Session 3-- Extracellular Matrix and Morphogenesis, Program #2003, Board #B382, Exhibit Halls D-H.