Making Strides in Regenerative Medicine
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An interview with Dr. William Murphy, Professor, Biomedical Engineering, Orthopedics & Rehabilitation, and Co-director, Stem Cell & Regenerative Medicine Center, University of Wisconsin.
Dr. Murphy tells us a little about his career and the work his lab is doing to develop biomaterials and help advance the regenerative medicine field.
AM: How did you become interested in science and stem cell research in particular?
WM: Like many scientists, I have been interested in science since I was a young child. It has always been fascinating to me how the world works, and particularly the kinds of exquisite patterns that exist throughout nature. I have been particularly interested in the materials that nature can produce, which often have properties that we can try to mimic as we create artificial “biomaterials”. My interest in biomaterials ultimately led me to regenerative medicine, which involves trying to regenerate human tissues to both understand and treat human diseases. Combining biomaterials with stem cells is particularly powerful, since stem cells are able to produce human tissues, and biomaterials can help provide the blueprints for construction of human tissues.
AM: What have some of your most rewarding achievements been so far?
WM: The most rewarding work we have done is the work that is closest to impacting patients. In one area, we have developed medical devices that can be implanted into a defect, dissolve over time, and get replaced by new, functional tissue. One example is a class of 3-D printed polymer “scaffolds” that can be placed into large bone defects and encourage bone regeneration. These devices are FDA approved for some applications, and are being developed as clinical products to treat bone defects in multiple clinical areas. In another area, we have developed miniscule human tissues-on-a-chip, which can be used to discover new drugs and test for possible environmental toxins. Usually scientists use animals like mice to test new drugs or potential toxins, and obviously humans are different from mice. Some of our human tissues-on-a-chip might ultimately replace mice and other animals, and allow us to discover better drugs faster.
AM: Can you tell us about your lab's main research directions?
WM: We are developing biomaterials to understand and manipulate stem cell behavior. One focus area is “biomanufacturing”, where we are using biomaterials as tools to more efficiently produce cells that can be useful as new medicines. Another focus area is regenerative medicine, where we are implanting biomaterials and designing them to control new tissue regeneration.
AM: What are some of the limitations of current cell manufacturing processes?
WM: Reproducibility, scalability, and cost. Some diseases will require that we deliver billions of cells to each patient, so it is not inconceivable that we will need to be able to produce billions-trillions of a particular cell type. Obviously the cells need to be the same at the end of each manufacturing process, and the costs need to be minimized. Another area that is absolutely critical, and perhaps underappreciated, is delivery. Many of the studies performed to date simply involve injecting cells into the bloodstream and hoping that they will go to the site of damage or disease. If we can more effectively deliver therapeutic cells we will likely improve the success of clinical trials.
Human fibroblasts growing on a parsley plant. Credit: William Murphy
AM: Can you tell us about the biomaterials that your lab and Stem Pharm are creating to improve this process?
WM: We are developing biomaterials that are customized for production of therapeutic cells and tissues. One technology platform is customized hydrogels, which are similar to Jello in consistency but obviously very different in their chemical composition. We can design the hydrogels to have just the right properties to encourage stem cells to multiply, differentiate into other useful cell types, or assemble into human tissues. One example is a hydrogel that allows for assembly of blood vessel networks from human stem cells. Another technology platform involves using mineral-based biomaterials to deliver genes to cells. Here we can re-wire cells on the inside, and thereby manufacture cells that have specific properties. One example involves delivery of genes that can “re-program” cells from the skin of a patient into cell therapies. The goal is to be able to take cells from a patient and manipulate them to create new medicines for untreatable diseases.
AM: What implications could this technology have in the regenerative medicine field?
WM: Our biomaterials can be enabling throughout regenerative medicine. They can allow companies to manufacture and deliver cells more effectively, which will make these therapies more practical. They can also deliver other biologics more efficiently, including small molecules, peptides, proteins, RNA, and DNA. These approaches will allow us to “activate” tissue regeneration in new ways.
AM: What future work do you have planned?
WM: There are lots of directions that extend from our recent work. Cell manufacturing can be scaled and controlled in a variety of innovative ways, and one of our most recent approaches even uses biofunctionalized plants as scaffolds to manufacture human stem cells. Another particularly exciting area is in disease modeling. There are developmental disorders, such as autism spectrum disorders, that are not well-understood. We can use our human brain-on-a-chip models to learn more about these conditions, and eventually help to develop new medicines to treat the conditions. Finally, an area that is rapidly emerging involves transforming patient-derived tissues into different, and more useful, therapeutic tissues. For example, we are working on transforming common blood clots into functional bone and cartilage tissue. The idea of getting therapies directly from the patient to be treated (rather than from a donor) has obvious advantages.
