Week in BioE (October 30, 2017)

Using Stem Cells to Repair Damaged Tissue

CCND2
Induced pluripotent stem cells

Repairing heart tissue after a heart attack is a major focus of tissue engineering. A key challenge here is keeping grafted cardiomyocytes in place within the tissue to promote repair. As we reported a couple of weeks ago, using tissue spheroids and nanowires is one approach to overcome this challenge. Another approach involves manipulating the cell cycle — the process by which normal cells reproduce, grow, and eventually die.

In the latest advance in cellular engineering for this purpose, Jianyi Zhang, M.D., Ph.D., chair of the Department of Biomedical Engineering at the University of Alabama, Birmingham (UAB) and T. Michael and Gillian Goodrich Endowed Chair of Engineering Leadership, published an article in Circulation Research showing how to control key cell-cycle activators to improve the success rate of cardiomyocyte transplants. Dr. Zhang and his coauthors, using a mouse model of myocardial infarction, engineered the transplanted cells so that they expressed much higher levels of cyclin d2, a protein that plays a key role in cell division. Cardiac function improved significantly, and infarct size decreased in mice receiving these engineered the cells. The authors plan to test their discovery next in larger animal models.

Use of stem cells in tissue regeneration isn’t limited to the heart, of course. Stephanie Willerth, Ph.D., Canada Research Chair in Biomedical Engineering at the University of Victoria in Canada, is one of two recipients from that school of an Ignite Award from the British Columbia Innovation Council. Dr. Willerth will use her award to create “bioink” for three-dimensional printers. The bioink will convert skin cells into pluripotent stem cells using technology developed by Aspect Biosystems, a biotech company in Vancouver. Once induced, the pluripotent stem cells can be converted again into a number of different cell types. Dr. Willerth’s specific focus is building brain tissue with this technology.

Making Music

Prosthetic limbs have been a standard of care for amputees and people with underdeveloped arms or legs. Many current prostheses are designed to resemble actual limbs and use myoelectrical interfaces to re-create normal movements. Alternatively, other prostheses designed for specific purposes, such as the Flex-Foot Cheetah prosthetic foot for running, do not resemble the human limb but are optimized for a specific prosthetic function.

Now, a group of undergraduate bioengineering students at George Mason University (GMU) produced a prosthetic arm to play the violin. The students, who were instructed by Laurence Bray, Ph.D., associate chair of the Department of Bioengineering at GMU, were connected with a local fifth grader from nearby Alexandria, Va., named Isabella Nicola. Nicola was born without a left hand and only part of her left arm, and she had been learning violin using a prosthesis designed for her by her music teacher. The teacher, a GMU alumnus, reached out the department for help.

The design team used a three-dimensional printer to create a prosthetic arm for Isabella. The prosthesis is made of durable, lightweight plastic and includes a built-in bow, which Isabella can use to play her instrument. The prosthesis is hot pink — the color of Isabella’s choosing. She can now play the violin much more easily than before. Whether a symphony chair is in her future is up to her.

People and Places

The University of New Hampshire will use a five-year Center of Biomedical Research Excellence grant by the National Institutes of Health to create the Center of Integrated Biomedical and Bioengineering Research. The center will unite several colleges under the rubric of bioengineering and biomedical engineering. Similarly, the University of Iowa will use a $1.4 million grant from the Roy J. Carver Charitable Trust, an Iowa-based charity, to add a biomedical engineering laboratory for its College of Engineering.

Finally, congratulations to University of Minnesota Ph.D. BME student Lizzy Crist, who has been named the NCAA’s Woman of the Year, for her undergraduate record as a scholar-athlete (soccer) at Washington University in St. Louis.  She joins last year’s winner, MIT biological engineering student Margaret Guo, a swimmer who is now an M.D./Ph.D. student at Stanford.

Week in BioE (August 25, 2017)

Beyond Sunscreen

skin cancer
The sun

Excessive exposure to the sun remains a leading cause of skin cancers. The common methods of protection, including sunscreens and clothing, are the main ways in which people practice prevention. Amazingly, new research shows that what we eat could affect our cancer risk from sun exposure as well.  Joseph S. Takahashi, Ph.D., who is chair of the Department of Neuroscience at the University of Texas Southwestern Medical Center’s Peter O’Donnell Jr. Brain Institute, was one of a team of scientists who recently published a paper in Cell Reports that found that by restricting the times when animals ate, their relative risk from exposure to ultraviolet light could change dramatically.

We tend to think of circadian rhythms as being among the reasons why we get sleepy at night, but the skin has a circadian clock as well, and this clock regulates the expression of certain genes by the epidermis, the visible outermost layer of the skin. The Cell Reports study found that food intake also affected these changes in gene expression. Restricting the eating to time windows throughout a 24h cycle, rather than providing food all the time, led to reduced levels of a skin enzyme that repairs damaged DNA — the underlying cause of sun-induced skin cancer. The study was conducted in mice, so no firm conclusions about the effects in humans can be drawn yet, but avoiding midnight snacks could be beneficial to more than your weight.

Let’s Get Small

Nanotechnology is one of the most common buzzwords nowadays in engineering, and the possible applications in health are enormous. For example, using tiny particles to interfere with the cancer signaling could give us a tool to stop cancer progression far earlier than what is possible today. One of the most recent approaches is the use of star-shaped gold particles — gold nanostars — in combination with an antibody-based therapy to treat cancer.

The study authors, led by Tuan Vo-Dinh, Ph.D., the R. Eugene and Susie E. Goodson Professor of Biomedical Engineering at Duke, combined the gold nanostars with anti-PD-L1 antibodies. The antibodies target a protein that is expressed in a variety of cancer types. Focusing a laser on the gold nanostars heats up the particles, destroying the cancer cells bound to the nanoparticles. Unlike past nanoparticle designs, the star shape concentrate the energy from the laser at their tips, thus requiring less exposure to the laser. Studies using the nanostar technology in mice showed a significant improvement in the cure rate from primary and metastatic tumors, and a resistance to cancer when it was reintroduced months later.

Nanotechnology is not the only new frontier for cancer therapies. One very interesting area is using plant viruses as a platform to attack cancers. Plant viruses stimulate a natural response to fight tumor progression, and these are viewed by some as ‘nature’s nanoparticles’. The viruses are complex structures, and offer the possibility of genetic manipulation to make them even more effective in the future. At Case Western Reserve University, scientists led by Nicole Steinmetz, Ph.D., associate professor of biomedical engineering, used a virus that normally affects potatoes to deliver cancer drugs in mice. Reporting their findings in Nano Letters, the authors used potato virus X (PVX) to form nanoparticles that they injected into the tumors of mice with melanoma, alongside a widely used chemotherapy drug, doxorubicin. Tumor progression was halted. Most importantly, the co-administration of drug and virus was more effective than packing the drug in the virus before injection.  This co-administration approach is different than past studies that focus on packaging the drug into the nanoparticle first, and represents an important shift in the field.

Educating Engineers “Humanely”

Engineering curricula are nothing if not rigorous, and that level of rigor doesn’t leave much room for education in the humanities and social sciences. However, at Wake Forest University, an initiative led by founding dean of engineering Olga Pierrakos, Ph.D., will have 50 undergraduate engineering students enrolled in a new program at the college’s Downtown campus in Winston-Salem, N.C. The new curriculum plans for an equal distribution of general education/free electives relative to engineering coursework, with the expectation that the expansion of the liberal arts into and engineering degree will develop students with a broader perspective on how engineering can shape society.

People in the News

At the University of Illinois, Urbana-Champaign, Rashid Bashir, Ph.D., Grainger Distinguished Chair in Engineering and professor in the Department of Bioengineering, has been elevated to the position of executive associate dean and chief diversity officer at UIUC’s new Carle Illinois College of Medicine. The position began last week. Professor Michael Insana, Ph.D., replaces Dr. Bashir as department chair.

At the University of Virginia, Jeffrey W. Holmes, Ph.D., professor of biomedical engineering and medicine, will serve as the director of a new Center for Engineering in Medicine (CEM). The center is to be built using $10 million in funding over the next five years. The goal of the center is to increase the collaborations among engineers, physicians, nursing professionals, and biomedical scientists.

Macrophages Engineered Against Cancer Cells

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Dennis Discher, Ph.D.

Dennis E. Discher, Ph.D., Robert D. Bent Professor in the Department of Chemical and Biomolecular Engineering and a secondary faculty member in the Department of Bioengineering, was the lead author on a recent study that showed that engineered macrophages (a type of immune cell) could be injected into mice, circulate through their bodies, and invade solid tumors in the mice, engulfing human cancers cells in the tumors.

According to Cory Alvey, a graduate student in pharmacology who works in Professor Discher’s lab and the first author on the paper, said, “Combined with cancer-specific targeting antibodies, these engineered macrophages swarm into solid tumors and rapidly drive regression of human tumors without any measurable toxicity.”

Read more here.

How Cells Spread in Fibrous Environments

New research by faculty in the University of Pennsylvania Department of Bioengineering is examining the interplay between cells and their environment and how they impact the cells’ ability to grow and spread, showing that stiffness is not the only factor researchers should consider when studying this process.

The relationship between cellular adhesion and spread is a key factor in cancer metastasis. Better understanding of this dynamic would improve diagnosis of the disease and provide a potential target in combating it; reducing the ability of cells to grip their environment could keep them contained.

 

fibrous environemnts
Vivek Shenoy (left) and Jason Burdick

The study, published in the Proceedings of the National Academy of Sciences, was led by Vivek Shenoy, professor in the Department of Materials Science and Engineering, co-director of Penn’s Center for Engineering Mechanobiology, and a secondary faculty member in the Department of Bioengineering, along with Xuan Cao and Ehsan Ban, members of his lab. They collaborated with Jason Burdick, professor in the Department of Bioengineering, Boston University’s Christopher Chen, the University of Michigan’s Brendon Baker and the University of Hong Kong’s Yuan Lin.

This collaboration reflects work of The Center for Engineering Mechanobiology, a National Science Foundation-funded Science and Technology Center that supports interdisciplinary research on the way cells exert and are influenced by the physical forces in their environment.

​​​​​​​Previous work from Shenoy’s group has shown that the relationship between cancer cells and the extracellular matrix is dynamic, containing feedback mechanisms that can change the ECM’s properties, including overall stiffness. One earlier study investigated how cancer cells attempt to strike a balance in the density of the fibrous netting surrounding them. If there are too few fibers to grip, the cells can’t get enough traction to move. If there are too many, the holes in the net become too small for the cells to pass through.

Read more at the Penn Engineering blog.