Engineering Stem Cells as a Therapy for Immune Disease

What biomedical issue did you address in your research and what did your studies find?

My research focused on addressing autoimmune and immune-mediated diseases, which are increasingly prevalent in the U.S. Current treatments often focus on managing symptoms rather than addressing root causes of immune inflammation. One approach under investigation is the use of mesenchymal stromal cells, or MSCs, a type of stem cell that can be isolated from fat tissue. These cells have the potential to promote regeneration of injured tissue and to modulate the immune system by immunosuppression. They also prompt less reaction from the immune system than other types of treatments when administered off-the-shelf. However, MSC therapies have shown limited efficacy in the clinic. They elicit a weak immunosuppressive response in patients and are poorly trafficked between the tissues of the body once administered. 

Our lab works on cellular engineering, redesigning cells from the body to be better equipped to fight disease. To address immune-mediated diseases, we designed and reengineered MSCs to express proteins known as chimeric antigen receptors (CARs), like the successful CAR T-cell therapies used in cancer treatment. We created CAR-MSCs to enhance both tissue trafficking and immunosuppressive activation to protect critical organs from immune attack. This is especially relevant in conditions like graft-versus-host disease (GvHD), when donated cells from a stem cell or bone marrow transplant attack healthy tissue. Compared to nonengineered MSCs, our CAR-MSC therapy enhanced therapeutic outcomes in preclinical models of GvHD, including reduced symptoms, prevention of weight loss, reduction in cytotoxic T cells and prolonged survival. In addition, our CAR-MSCs showed increased trafficking to CAR-specific disease sites and enhanced immunosuppressive activity. Our results, published in Nature Biomedical Engineering, suggest that CAR-MSC therapy could be a promising therapeutic approach for treating immune diseases. Excitingly, the CAR-MSC therapy we designed is being translated for a Phase 1 clinical trial at Mayo Clinic for patients with steroid-refractory acute GvHD, a life-threatening condition that can occur in patients following a stem cell transplant.

What aspects of your training at Mayo helped you grow as a scientist and as a thinker?

I had the opportunity to serve as a student course director and created a course focused on regenerative immunotherapy. Working with more than 30 experts in their fields, I helped develop a comprehensive course structure for Mayo graduate students. I also had the chance to do a translational industry internship at Genentech during my Ph.D. training. For the internship, I moved to San Francisco and experienced working in biotech, completing projects on biologics in Phase 1 clinical trials. This experience solidified my future career goals in the translational medicine space.

What's next?

The graduate school connected me with a lab "family" made up of individuals from all over the world. In this environment, I’ve learned vast amounts of scientific knowledge, how to communicate my work to others, and how to optimize my scientific writing and problem-solving. My experience training in a translational lab at Mayo exposed me to how the biotherapeutic industry works and has inspired me to pursue a career in the pharmaceutical industry.