Regenerative Medicine Lab Grows Muscoskeletal Tissues from Stem Cells

Everything's coming up bone, cartilage, tendons, and ligaments in the lab of Wan-Ju Li, PhD.


Dr. Li, an assistant professor of orthopedic surgery and biomedical engineering, uses electrospinning - a technology developed in 1934 for weaving fiber into textiles - to create intricate scaffolds that mimic human collagen. He then cultures adult stem cells in those scaffolds so they can grow into mature, functional tissue.


The goal? Someday, these custom-engineered tissues could be implanted into injured and arthritic joints, helping patients lead healthier, pain-free lives.


Hybrid Research Focuses on Cells and their Environment


The highly recruited Dr. Li came to the University of Wisconsin-Madison almost two years ago, after completing a postdoctoral fellowship at the National Institutes of Health.


He currently leads the Laboratory of Musculoskeletal Biology and Regenerative Medicine in the University of Wisconsin School of Medicine and Public Health. Since the lab's creation in September 2008, Dr. Li has recruited 11 talented, postdoctoral fellows, graduate students and undergraduate students to work on orthopedic regenerative medicine research.


Funding has come from multiple research grants from the North American Spine Society and the AO Foundation, a non-profit organization dedicated to improving the care of patients with musculoskeletal injuries.


With education in both biomedical engineering and cell biology, Dr. Li is a "hybrid" scientist whose cutting-edge work approaches tissue engineering from both the cellular and the biomaterial perspectives.


For example, one arm of his research aims to optimize the process for growing tissue from stem cells: the "holy grail" of tissue engineering. He has already shown this method works in pig bone and cartilage, and is collaborating with researchers at the UW School of Veterinary Medicine to test engineered cartilage, tendon and intervertebral discs function in a sheep model.


But Dr. Li is also studying how scaffold structure affects cell activity. Questions include: how does the scaffold's microstructural features, such as dimension, affect the cellular response; which cell receptors and signaling pathways are activated; and which genes turn on in response to the new environment?


He has cultured stem cells in both 2-D and 3-D scaffolds, and then extracted the cells and globally profiled 38,500 genes in microarrays to learn which genes are turned on and off in the 2-D and 3-D groups.


"Environmental setup affects the cells dramatically, just like housing atmosphere and architecture affects the human beings living there," explained Li. "We want to make sure that the humans living in the house are happy and function normally. That is the way to think about designing a scaffold - to make the cells sitting in the scaffold happy and able to respond and produce the matrix."


Dr. Li's research has generated two patents and produced nearly 30 publications, including one cited more than 500 times in eight years.


Collaboration Thrives at WIMR


Dr. Li's lab is based at the Wisconsin Institutes for Medical Research (WIMR), a multidisciplinary center that brings together basic and clinical research talent to tackle medicine's most important questions.


The collaborative environment at WIMR is essential for Dr. Li's research. He needs to work closely with cell biologists, engineers and transplant and orthopedic surgeons to quickly get their unique perspectives and then get his lab findings to people who need it.


The WIMR facility eliminates laboratory walls, places office areas close to labs, allows rapid sharing of complex equipment and facilities, and includes interactive space on every floor. Dr. Li says WIMR is one reason he wanted to come to Wisconsin over other institutions.

"The collaboration is already happening for my lab. When I need bone marrow [from which to isolate adult stem cells], I can just talk to my colleagues next door."