Research Team Develops 3D Tissue Model of Developing Human Heart

The heart is the first organ to develop in the womb and the first cause of concern for many parents.

Four people in lab coats, two sitting at microscopes

Zhen Ma, rear, with his research team

For expectant mothers, the excitement of pregnancy is sometimes offset by anxiety over medication they require. Parents and doctors often have to consider the mother’s health as well as the potential risk of how medication could affect the baby. The U.S. Food and Drug Administration requires certain drugs to be labeled regarding pregnancy exposure and risk. Some drugs are labeled to show that testing on animals has failed to demonstrate a risk, but there are no adequate and well-controlled studies of pregnant women.

“Some drugs are difficult for doctors to prescribe to pregnant women because they don’t know the embryo toxicity, how does that effect fetal development,” said biomedical engineering Assistant Professor Zhen Ma. “They don’t have the clinical outcome based on human study.”

Ma and his research team in the System Tissue Engineering & Morphogenesis (STEM) lab have been working with human-induced pluripotent stem cells to study tissue regeneration, regenerative medicine and stem cell engineering.

“This type of stem cell has the ability to generate all the different cells in a human body. Because it was derived from humans,” says Ma.

Pluripotent cells can be used to create heart tissue, but Ma’s research team believed they could take it even further.

“We can try to rebuild the shape of the early development heart in the lab,” says Ma. “It mimics the very early stage, during the embryo genesis—how the heart was formed.”

Ma’s research team developed a process that combines biomaterials-based cell patterning and stem cell technology to make a 3D tissue model that could mimic early stage human heart development. By starting with a layer of polymer in a tissue culture dish and etching tiny patterns in the polymer, the stem cells will only attach within those patterns. Since the stem cells do not attach to the polymer, they grow within the patterns and eventually develop into a three-dimensional structure that has distinct tissue types. The process developed by Ma’s team focused on cardiac tissue, but other labs could adapt it to other tissue types and even organ tissues.

Their research was published in the March 2018 Nature Protocols journal and featured on the cover.

The platform allows tissue to form during the cell differentiation process rather than building tissue out of already-established heart cells. Tissue that forms during the differentiation process has more layers and more accurately represents how tissue naturally develops in humans.

“Using the cell lines we use, they are human based so we know they will affect human tissue in a certain way as opposed to the uncertainty that comes with an animal model,” says graduate student Plansky Hoang.

Some pregnant women avoid taking drugs they need to manage chronic conditions, but if the mother’s health suffers, that can also affect her baby. More reliable test results could provide more confidence for both patients and doctors.

“It helps people make better decisions,” says Ma. “If we can determine it is safe, it should be prescribed to women who need these drugs.”

Embryotoxicity is just one potential use of the modeling platform developed by Ma and his team. Countless other human tissues could also be cultured using the process. It could also allow for individualized drug toxicity testing for humans. Different people can have different reactions to the same drug but personalized testing using someone’s stem cells could help determine if a drug is safe for them before they take it.

“The traditional way of screening, they take a patient history and then test you on a drug for a month or two and they assess again you after that,” says Hoang. “By using our model we can test for multiple drugs at once, so if there is a series of drugs that will potential benefit you, we can test all of them at once as opposed to one at a time that takes longer.”

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How to Fix a Broken Heart

An article on SLM Faculty member, Zhen Ma appears on  Read the full story here.

Through stem cell research in his Syracuse Biomaterials Institute lab, Professor Zhen Ma and his team are growing human hearts so they can find better ways to fix them when they break.

SLM Director Named to Commission on Statistical Physics

Distinguished Professor M. Cristina Marchetti has been elected to the Commission on Statistical Physics as part of a select group of international scientists.

The Commission on Statistical Physics (C3) was established by the International Union of Pure and Applied Physics (IUPAP) in 1945 to promote the exchange of information and views among the members of the international scientific community in the general field of statistical physics.

Marchetti, the William R. Kenan Distinguished Professor of Physics in the College of Arts and Sciences, was nominated for the position and elected by the commission members.

“This new leadership role continues Cristina’s incredible record as a leader in scientific societies, meetings and journals,” says A. Alan Middleton, associate dean of research and scholarship and professor and chair of the Department of Physics. “She has not only contributed at the highest levels as a formal leader, conference organizer and editor, but she has also led in initiating new divisions within societies, such the Topical Group on Soft Matter in the American Physical Society. She is well known around the world for her research and leadership in statistical physics.”

Marchetti’s research for the past 25 years has spanned a broad range of problems in statistical physics and soft matter, from superconductivity to biological physics, with a focus on nonequilibrium phenomena.

“In recent years my work has focused on the emergent behavior of ‘active matter,’” Marchetti says. “The name describes collections of self-driven entities that exhibit organized behaviors on scales much larger than that of the individuals—examples range from the flocking of birds to the sorting and organization of cells in morphogenesis [the biological process in which an organism develops its shape], and include synthetic analogues, such as engineered microswimmers.”

In 2016, Marchetti was granted a major award from the National Science Foundation for $420,000 to pursue the research.

With the breadth of her background and research, Marchetti hopes to bring to the commission “a deep appreciation for the diversity of the field of statistical physics and of its connection to other areas of physics and to other disciplines.”

Marchetti also sees the need for enhanced unity and visibility for statistical physics and its relevance to many areas of science and engineering. “This can only come from better communication across disciplinary and national boundaries, and IUPAP can play a key role in this effort,” she says.

Marchetti has also served in the soft matter and statistical physics community in various roles, including as elected chair of the American Physical Society Topical Group on Statistical and Nonlinear Physics and currently as chair of the recently formed Topical Group on Soft Matter (GSOFT). She has also organized conferences; served on selection committees for international prizes; and is the co-lead-editor of Annual Reviews of Condensed Matter Physics and Physical Review X.

As a mentor and teacher, Marchetti is deeply committed to increasing diversity among faculty and students in the sciences and strengthening graduate education and providing students with exposure to and appreciation for the interdisciplinarity of soft materials physics and the broad relevance of statistical physics. She has propelled new models of graduate education at Syracuse and nationally as one of four principal investigators running the Boulder Summer School for Condensed Matter and Materials Physics.


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