Biomedical engineer is developing heart-tissue regeneration process - CTTEC - Carnegie Mellon University

Monday, October 1, 2012

Biomedical engineer is developing heart-tissue regeneration process


Contrary to the pop-song lyric, time cannot heal the damaged heart.

Impaired by disease or injury, the heart and other internal organs neither replace themselves as happens with the salamander's tail nor repair themselves the way human skin and bones do.

That's where Carnegie Mellon University's Adam W. Feinberg makes his entrance with a novel strategy that uses biological materials he's developing to mend a broken heart.

He's developing a heart-tissue regeneration process inspired by the growing human embryo -- the only stage in human life when the complex architecture of heart muscle tissue actually is created. Replicating those principles without using actual embryo tissue to avoid controversy, he's developing a repair kit of artificially produced protein framework and genetically engineered cells to repair heart injury and disease.

The futuristic idea of using biological materials mimicking the embryo, and using the process in other areas of the body, is drawing attention.

Mr. Feinberg, an assistant professor with a doctoral degree in biomedical engineering, has received a $2.25 million National Institutes of Health Director's New Innovator Award, to be paid over five years, to develop biomaterials and procedures to engineer muscle tissue for repairing the heart. He's working on a similar repair process for the cornea.

He's one of 81 researchers nationwide this year -- and the first CMU researcher -- to receive funding through the NIH's High Risk-High Reward program created in 2007. The award allows researchers to pursue visionary science with potential to transform scientific fields and hasten the process of converting research into improved health, a university news release states.

Vijaykumar Bhagavatula, interim dean of CMU's College of Engineering, praised Mr. Feinberg's research vision and drive to push the research envelope.

Mr. Feinberg's article -- published this year in the Wiley interdisciplinary review publication Systems Biology and Medicine -- says engineered tissue grafts hold tremendous promise to regenerate a variety of tissues and organs in the body, with added opportunity "to patch the diseased or damaged region before the remaining, intact tissue begins to undergo pathological changes."

Researchers worldwide are focused on tissue regeneration, including those at UPMC and the University of Pittsburgh's McGowan Institute for Regenerative Medicine. Their traditional top-down approach involves using actual extracellular matrix that's made by removing all cells mostly from pig tissue to produce the protein scaffolding that supports tissue. Other researchers are experimenting with synthetic matrices.

What might sound like science fiction, Mr. Feinberg and his research team are creating heart matrix from scratch, putting it together from the bottom up in their CMU laboratory.

The developing embryo's matrix consists of fibrous proteins -- collagen, elastins and other supportive structures -- in a unique pattern that uses growth factors and other elements to make cells form tissue, muscle and the entire heart. Once the heart is fully developed, the matrix changes its pattern to support the tissue but loses the ability to regenerate damaged muscle.

Mr. Feinberg will study formation of the embryo's matrix by using fluorescent labels to mark proteins and observe them under a powerful 3-D microscope. Results, downloaded into a computer, produce a 3-D model of how the matrix forms during cardiac development. That's the process he hopes to replicate.

"We mimic the way cells make these protein fibers," he said. Cotton or polyester fibers are spun to form clothing, but cells build protein fibers on the surface of their membranes. He's mimicking that process to create sheets of matrix comparable to that in the embryonic heart.

"We will be ultimately applying this basic research to model how cells interact with the extracellular matrix in multiple tissue types, including cornea and cardiac muscle," he said. "Future medical applications include improved drug discovery and screening platforms, novel tools for biological investigation and engineered tissue grafts for disease and trauma repair.''

Making muscle cells -- human cardiomyocytes that form the heart -- soon will be under way in his lab.

He's working to coax adult-derived stem cells that behave like embryonic stem cells to become heart muscle cells. But getting those cardiomyocytes to turn from a pile of cells into healthy heart muscle that can contract and pump blood remains the big challenge. Once he has the building blocks that mimic embryonic tissue, he'll seed the artificial matrix with the created cells to generate heart-like muscle tissue that eventually could be used to repair the heart or gauge how the tissue responds to drugs.

"I am extremely excited about this award because it will allow me to continue pursuing leading edge research designed to help regenerate and repair heart muscle and improve wound healing in a variety of biomedical arenas,'' Mr. Feinberg said.

Christine L. Mummery, a developmental biologist and chairwoman of the Leiden University Medical Center's Department of Anatomy & Embryology in The Netherlands, said she's "a great fan of Adam's research."

"He is a very innovative engineer who is able to combine his knowledge of materials with cells of the heart in such a way that building synthetic heart tissue is a step nearer," she said, noting its potential beyond heart repair.

"This is often the reason that new drugs fail to reach the clinic or are withdrawn -- negative side effects on the heart," Ms. Mummery said. "Having synthetic heart tissue in the lab that is able to undergo normal stretching and contraction of the real human heart will ultimately be a great help in dividing new drugs into those that are safe and those that could have a high risk."

Harvard University bioengineer Kevin Kit Parker said Mr. Feinberg "was a spectacular post-doctoral fellow" in his research group with "great expertise in material science."

"CMU is lucky to get him, and NIH was wise to give him the grant. It's wise use of taxpayers' dollars," he said. "Adam adds another piece to the puzzle of a very elite community of regenerative medicine researchers.

"There's a high probability of him being a leader in the field, and in that regard he will distinguish himself," Mr. Parker said, noting that Mr. Feinberg is "one of three or four people in world qualified to do the research. "It's a narrow population of people with an understanding of biomaterials, and Adam is one of them."



Article courtesy of Pittsburgh Post-Gazette