April Craft, Ph.D., an HSCI Principal Faculty member, is using stem cells to investigate exactly how joint tissues form. Armed with precise knowledge about healthy tissue development, her lab at Boston Children’s Hospital has set out to radically improve joint repair.
“Cartilage is unable to repair itself after injury, and most of us, especially athletes, appreciate how serious this can be for overall joint health. To alleviate pain associated with cartilage damage and promote repair, many patients undergo a treatment called microfracture, but the fibrocartilage-like tissue that forms in the joint is not ideal. I think it’s within reach to create a stem cell-based solution that will finally provide patients with pain-free, long-term joint movement,” Craft said.
An initial seed grant from HSCI enabled Craft to optimize her tissue-engineering approach to ensure it is reproducible and easy to control. Thanks to funding for a full pilot study in 2019, she is now testing whether her stem cell-based cartilage tissue can repair joints in a pig model.
“Support from the HSCI has been instrumental for our translational work. This preclinical study in large animals will allow us to demonstrate that a stem cell-based cartilage implant will heal joints better than the existing treatment options available for patients. We are optimistic that we can move this discovery towards clinical care through collaborations with industry and venture partners,” she said.
Craft expects progress towards clinical application to be rapid because many of the pieces are already in place: cell collection, tissue manufacturing, and surgical implementation pipelines are already well established. With some adjustments, that pipeline could well accommodate a stem cell-derived product.
“We are infinitely motivated to translate stem cell discoveries because they have great potential to help patients in need, perhaps much sooner than anyone realized. The grant from HSCI allowed us to transition from repairing cartilage in rat to pig, and to attract one of the best orthopedic and sports medicine surgeons to join our efforts. Having support from the greater stem cell community builds confidence within our group that what we are doing will benefit patients in the near future,” she said.
In 2019, Craft joined HSCI Executive Committee members Jenna Galloway, Ph.D. of Boston Children’s Hospital and Vicki Rosen, M.D., Ph.D. of the Harvard School of Dental Medicine in launching the new HSCI Musculoskeletal Disease Program.
Aging, blood, and fibrosis research: Suneet Agarwal, M.D., Ph.D. of Boston Children’s Hospital, “Enhancing stem cell self-renewal via novel telomerase modulators” and Zhixun Dou, Ph.D. of Massachusetts General Hospital, “Empowering immunotherapy to treat age-associated diseases”
Nervous system disease research: Rakesh Karmacharya, M.D., Ph.D. of Massachusetts General Hospital, “Modeling synpatic pruning in schizophrenia with iPSC-derived microglia and neurons” and Mustafa Sahin, M.D., Ph.D. of Boston Children’s Hospital, “Examining non-cell autonomous effects in Tuberous Sclerosis Complex using neuronal spheroids from human iPSCs”
Cancer research: Ruben Carrasco, M.D., Ph.D. of Dana- Farber Cancer Institute, “Mining the Wnt/β-catenin/BCL9 transcriptional complex for gastric cancer pathogenesis and therapy”
Cardiovascular disease research: Elliot Chaikof, M.D., Ph.D. of Beth Israel Deaconess Medical Center, “Immuno-evasive engineered living blood vessels”
Musculoskeletal disease research: April Craft, Ph.D. of Boston Children’s Hospital, “Testing efficacy of hESC-derived cartilage in large animal model”
Lung disease research: Hongmei Mou, Ph.D. of Massachusetts General Hospital, “Regenerative capacity of human iPSC-derived airway basal cells”
Jorge Diego Martin-Rufino was in his fourth year of medical school in Spain when he decided to apply to the HSCI Internship Program (HIP). Drawn to the prospect of working in a cutting-edge stem cell research laboratory, he gained much more from the experience: inspiring mentorship, new perspectives on science and medicine, and a new direction for his career.
“Coming from medicine, I was really interested in the potential stem cells have for regenerative medicine, to restore damaged tissues and structures. My experience as a HIP intern allowed me to explore that, and was the most important factor in my decision to pursue a Ph.D. at Harvard Medical School. My goal now is to be a physician-scientist, combining my interests in hematology and genomics,” he said.
Martin-Rufino worked with Laurence Daheron in the HSCI iPS Core Facility and with HSCI faculty member Jerome Ritz at the Dana-Farber Cancer Institute, who provided mentorship and invited him to be part of a project to generate beta cells for replacement therapy in diabetes.
“The mentorship I received was amazing. Add to that all the biomedical infrastructure, and the connections between industry and the university and hospitals in the Boston area — it really sets it apart from other places. There is a strong focus on disease-oriented research at Harvard and HSCI, so for me it is a wonderful place to explore,” he said.
For Martin-Rufino, one of the greatest assets of the internship program is the sense of community, and the way it brings together people from many backgrounds.
“The combination of seminar series, lectures from top researchers, hands-on research, and shared experiences with fellow HIP interns was priceless,” he said. “The program shaped my approach to my career, and inspired me to become a physician-scientist. It is something I will never forget.”