November 20, 2023 | Office of the President & Chief Research Officer

Stanley Manne Children's Research Institute President's Message

Pioneering Regenerative Medicine at Lurie Children’s

and Manne Research Institute

Dear Teammates,


In the dynamic field of pediatric medicine, our focus often centers on the innate ability of children to heal and regenerate. This remarkable trait, most pronounced in neonates and young children, holds the key to transformative breakthroughs in regenerative medicine. At Manne Research Institute, we are deeply invested in unraveling these mechanisms, not only to advance pediatric healthcare but also to explore their potential in addressing diseases across the lifespan. The pioneering work of Youyang Zhao, PhD, Monica Laronda, PhD, and Arun Sharma, PhD, exemplifies our commitment to harnessing this knowledge for broader medical breakthroughs, offering hope for healing and recovery across all ages.


One remarkable approach to cell and tissue regeneration is reactivating the “master switches” for regeneration, which often become less active as we age. Youyang’s team is at the forefront of this field, uncovering the mechanisms that fuel intrinsic regenerative and repair processes early in life and exploring ways to reignite them after injury and older age. In the team’s latest study, featured in Science Translational Medicine, Youyang and colleagues made significant strides in understanding how the FoxM1 gene aids in repairing lung blood vessels damaged by sepsis. This is achieved through the regeneration of endothelial cells, which are crucial for maintaining the integrity and function of blood vessels. His team discovered that although the activity of the FoxM1 gene decreases with age, it can be reactivated. This reactivation is possible either through the administration of decitabine, a cancer treatment drug, or by employing a novel gene delivery technology targeted at the vascular endothelium, developed by Youyang and his team. These findings are pivotal, as Youyang believes that the future of regenerative medicine lies in tapping into and reactivating our body’s innate capacity for regeneration, a potential that diminishes with age, to facilitate natural recovery from various injuries.


Another innovative approach to regenerative medicine involves creating new tissues and organs using donor cells, which can be sourced either from the patients themselves or from unrelated donors. Monica, a renowned expert in reproductive biology and endocrinology, and her team are pioneering this approach with a focus on restoring fertility and hormonal functions in patients who have undergone treatments for cancer and other diseases. Her goal extends to developing an advanced ovary transplant that surpasses the capabilities of current ovarian tissue transplants. A testament to her team’s groundbreaking work is the development of a bioprosthetic ovary for mice. This bioprosthetic ovary, 3D-printed in a gelatin scaffold embedded with isolated follicles, has demonstrated remarkable success in restoring oocyte growth, fertility, and hormone production in mice missing their own ovaries. Currently, Monica and her team are collaborating with Dimension Inx, a biomaterials platform company, to push the boundaries further. Together, they are working on the next generation of 3D-printed scaffolds. These innovative scaffolds incorporate unique extracellular matrix proteins, specifically designed to stimulate the growth and maturation of follicles, potentially revolutionizing fertility treatments and paving the way for engineered ovaries ready for humans.


Leveraging his expertise in stem cell biology and regenerative engineering, Arun and his research group have made remarkable strides in the realm of urological tissue regeneration, particularly focusing on urinary bladder tissue. The team’s pioneering work holds the potential to create an alternative to the current practice of using bowel tissue for bladder tissue replacement. While the latter is the gold standard for treating severe bladder dysfunction, it often leads to several clinical complications. In the initial stages, the Sharma Laboratory made significant progress by developing a technique that involved harvesting autologous bone marrow stem and progenitor cells from consenting spina bifida patients at Lurie Children’s. These cells were then seeded onto a scaffold and grafted onto damaged bladders in a rodent model, effectively regenerating various aspects of bladder tissue. Following the publication of these promising results, Arun’s team ambitiously scaled up his research. Arun and colleagues have recently completed a study in a pre-clinical, large animal model, currently under peer review, which Arun anticipates will pave the way for a clinical trial in the near future. This work exemplifies our institute’s dedication to advancing regenerative medicine from theoretical research to practical, life-changing applications.


The groundbreaking research led by Youyang, Monica, and Arun at Manne Research Institute epitomizes the cutting-edge of regenerative medicine. As we forge ahead, their work not only symbolizes our unwavering commitment to innovative healthcare solutions but also underscores our potential to revolutionize medical treatments for both children and adults. With ongoing support and collaboration, we stand on the cusp of turning these scientific discoveries into tangible, life-enhancing therapies, marking a new era in medicine where regeneration and healing become a reality for many.

With kindness and respect,

Pat

Patrick C. Seed, MD, PhD, FAAP, FIDSA
President & Chief Research Officer
Stanley Manne Children’s Research Institute
Children's Research Fund Chair in Basic Science
Director, Host - Microbial Interactions, Inflammation, and Immunity (HMI3) Program
Professor of Pediatrics, Microbiology & Immunology
Northwestern University Feinberg School of Medicine
Ann & Robert H. Lurie Children’s Hospital of Chicago
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