yle Lampe, Assistant Professor of Chemical Engineering talks to ARI about regenerative medicine, biomaterials that heal, college towns and Maxwell’s equations.
In your research, you develop biomaterials to control the proliferation and fate of cells in the central nervous system. Can you explain a little about how that works?
Sure. In the lab we engineer hydrogels that reproduce many of the properties of native tissue. These hydrogels are made from different types of molecules – some are made from polymers like PEG and others are engineered from proteins like elastin. They are sort of like Jell-O and can encapsulate cells throughout them. In this environment, the stem cells can grow in three dimensions, as they would in a normal tissue environment.
So it sounds like these hydrogels mimic the stem cell niche or microenvironment?
That is right. And since the hydrogels are engineered, we can modulate their properties to influence the proliferation and the differentiation of the cells. You can watch a UVA video about the research in my lab and how we make use of the hydrogels.
What are some of the variables you can modulate?
Some of the variables that we tweak with the different biomaterials include their stiffness or the release of antioxidants over time, and biomaterials can also be used to target deliver of growth factors at a specific location and concentration.
So something as simple as how stiff the gel is affects the cell growth?
Absolutely. How tightly crosslinked the biomaterial is impacts how the cells will proliferate or differentiate along different paths. For instance, if the hydrogel is engineered stiffer, in the range of 30 kPa , neural stem cells will produce astrocytes and scar-like tissue will form. If the hydrogel is less stiff, like 1 kPa, neurons grow. Other types of cells can become bone, muscle, or fat depending on the material stiffness.
Is there a particular reason you focus on the cells of the CNS?
The kind of tissue engineering approach we take can be used to replace or regenerate many other tissues, including muscle, bone or the lining of the gut for example. But the cellular structures and tissues that make up the central nervous system are tricky to heal and present a really interesting challenge. The traditional interventions that work for other systems in the body are not possible in the CNS. You cannot stich a CNS injury site back together. An alternative approach is to fill in the injury site with the right kinds of cells and allow new functional tissue to grow to promote healing.
The CNS is very complicated and is comprised of many different cell types, with unique but integrated functions. This makes CNS tissue regeneration complicated. One big advantage of the approach we take is, that while we are working on engineering the biomaterials to have different properties, we are also learning new information about how the cells of the CNS grow and work together to function properly.
Can you tell us about one of your current projects?
One of the projects we are working on in the lab right now uses a poly(ethylene glycol) hydrogel. We are co-culturing neurons and the cells that produce myelin (oligodendrocytes) in this hydrogel to see if we can produce an environment where we will get the neuronal axons to be properly wrapped with myelin.
This particular research has ramifications for regenerative medicine in the treatment of diseases where myelin function is degraded, such as Multiple Sclerosis. But our work has applications for other neurological diseases, like Parkinson’s Disease, and for stroke and spinal cord injury too. There are also applications for wounded servicemen and women in regeneration of tissue and limb reconstruction.
How did you become interested in tissue engineering?
When I was an undergraduate, I participated in a summer research program, a NSF REU -Research Experience for Undergrads – at the University of Colorado, Boulder. I did my research in the Department of Chemical and Biological Engineering with a couple of professors including Kristi Anseth and I worked on a polymers project related to fillings for teeth. It was then that I first became fascinated by biomaterials. I decided to pursue graduate studies in the same department, with Melissa Mahoney, whose lab studies tissue engineering and the CNS. After graduating with my PhD, I did a post-doc with Sarah Heilshorn in Materials Science and Engineering at Stanford University.
Your research is very multi-disciplinary, involving biology, physics, chemistry and medicine.
I enjoy working at the intersections of all these fields. And UVa is a great place to do collaborative work. I have been here about a year and half and have already made some really great connections with other faculty in the UVa School of Medicine and the College of Arts and Sciences. Everyone is very open to working together, sharing reagents and technology. It is very collegial and supportive environment for me and the students in my lab.
Charlottesville is a great college town too. Having spent time in another great collage town, Boulder, my wife, Lisa, and I were excited to continue our careers in a college town with a great downtown mall and farmer’s market We live close enough to UVa that I can bike to work (when it’s not too hot!), and we like being so close to the Blue Ridge Mountains. Our dog, Maxwell seems to love it too.
What does your wife do?
Lisa works in the Office of Undergraduate Programs in the School of Engineering and she is the Director of Undergraduate Success. She ensures the engineering students have the academic resources and support that they need to do well at UVa. She also creates programming to help students develop skills they will need to complete an undergraduate degree in SEAS.
What kind of dog is Maxwell?
He is a rescued mutt, but we think mostly a beagle/dachshund mix. He is named after James Clerk Maxwell of Maxwell’s Equations. Lisa has her BS in applied mathematics and I’m a chemical engineer, so Maxwell seemed a good scientific compromise.
What is the biggest challenge facing the tissue engineering field?
A CNS stem cell niche is a very dynamic environment. There is a lot of going on. Growth factors are being secreted. Proteins in the extracellular matrix are being degraded and rebuilt. Other cells, like glial cells and endothelial cells, are present and they affect how the CNS cells develop. The chemistry of the niche, like the oxygen concentration, also changes and that impacts cell growth and differentiation. So engineering a microenvironment that really functions like the in vivo stem cell niche is a big challenge. And then figuring out which processes are critical for the purposes of clinical applications in regenerative medicine is a second challenge.
Thanks for talking with ARI. This was great.