July 8, 2024 | Office of the President & Chief Research Officer

Stanley Manne Children's Research Institute President's Message

The Future of Healing: Mapping New Frontiers in Tissue Repair and Regeneration

Dear Teammates,

Developing therapies that improve the body’s repair mechanisms requires a deeper understanding of the basic science behind the complex biological processes in injury repair and regeneration. The knowledge we generate at Ann & Robert H. Lurie Children’s Hospital of Chicago promises to profoundly affect how we treat certain diseases and congenital disorders. Leading these efforts within Manne Research Institute are Paul Schumacker, PhD, Patrick M. Magoon Distinguished Professor in Neonatal Research, and Arun Gosain, MD, Division Head of Plastic Surgery, whose exciting discoveries about how tissue repairs and regenerates may lead to therapies and better treatments for both children and adults.

Neonates have a remarkable capacity to repair damaged tissue in certain cases, but from childhood into adulthood, this capacity diminishes. For example, fetuses and newborns have a remarkable capacity to regenerate heart cells called cardiomyocytes that shuts down not long after birth. It is unknown why these cells lose this ability during development, but investigating how to successfully reactivate this process in post-natal or adult individuals when the cells are damaged is what Paul (pictured–right) calls “the holy grail of heart biology.” Solving this challenge can lead to new ways to treat children with congenital heart defects and adults who have suffered heart attacks. Through a series of research projects, Paul homed in on the role mitochondria play as the heart matures. He and his collaborators developed genetic models that allowed them to knock out a specific gene to disable the mitochondria in adult mouse cardiomyocytes. This forced the cells to revert their metabolism to what occurs in newborn cardiomyocytes, thereby recovering the ability to undergo cell division. When these mice were given a heart attack, just as the cells started to divide, projections of new cells penetrated the scar tissue, indicating that if you activate this cell division process when there is damage to the heart, there is potential for new cardiomyocytes to repair the damaged area. The next puzzle for researchers revolves around regulating cell regeneration. Paul hopes that future research into the mechanisms that turn off the ability of cardiomyocytes to divide continually will lead to the development of novel therapeutics that allow the heart muscle to regenerate after damage and then shut down the process of cell division.  

Our work in injury repair and regeneration also informs early life interventions that may help children with skull or facial abnormalities and children who have sustained traumatic injuries such as burns or animal bites. Fetal craniosynostosis is a congenital condition where fibrous joints called cranial sutures fuse prematurely in a fetus’s skull before the brain is formed, inhibiting normal skull development and brain growth. Arun (pictured–left) initially focused on studying the genetic mechanisms responsible for its development, examining the potential to alter the growth of the cells in the cranial sutures prenatally in zebrafish with the hopes that this may prevent the development of craniosynostosis. Success in this area has proven elusive, but the research has also followed an intriguing new investigatory path, examining the regenerative aspects of the tissue to improve tissue healing and make tissues more resilient after surgeries to treat craniosynostosis, facial abnormalities such as cleft lip and palate, and burns. Arun’s research team investigates the molecular mechanisms underpinning skin repair and growth in tissue expansion—a process where an expander device stretches existing skin to create skin for reconstructive surgeries. Using a porcine tissue expansion model, they are trying to identify the cellular and molecular processes that contribute to favorable tissue development to create tissue with an optimal healing environment that simulates the tissue healing process in neonates. Their current research shows promise in improving treatments for adult patients who have had a mastectomy for breast cancer and require further radiation therapy that may compromise the outcome of breast reconstruction surgery. In the future, they plan to use a tissue expansion model to create next-generation optimized tissue to replace damaged or congenitally abnormal tissue in pediatric patients, helping them heal better and faster after reconstructive surgeries than they do with current treatments and offering them the chance to live productive lives free of the social stigma of severe scarring that may result from radiation, trauma, or prior surgery.