New approaches to the study of human lung development are generating a fresh look at multiple considerations, from potential therapies to mechanisms that model development and disease. 

Tuesday’s session, Human Lung Development: New Tools and Therapeutic Strategies, explores various aspects of human lung development, including early branching, 2-D and 3-D in vitro culture models mimicking human development, the use of human lung iPSCs to model development and disease and the potential of stem cells as a therapeutic avenue for respiratory diseases. Each of these models is unique in its own way, allowing for the study of different key factors and pathways critical in lung development and disease. This includes Wnt and FGF signaling pathways, according to Denise Al Alam, PhD, assistant professor at The Saban Research Institute of Children’s Hospital in Los Angeles. 

“Lung diseases are among the leading causes of death in the United States, both in pediatric and adult populations,” Dr. Al Alam says. “Because of the rise in the survival rate of extremely premature infants, the number of patients with lung disease in this population has also been on the rise. Nine out of 10 clinical trials fail to reach the clinic. Therefore, progress in introducing new therapies for pediatric diseases has stalled significantly.”

Denise Al Alam, PhD

Recent studies suggest there are major differences between mouse models of diseases and human diseases, impeding the success of clinical trials. In addition to the structural, temporal, and scale differences between mouse and human lungs, newer studies have highlighted other major differences between mouse and human lung development. This knowledge can help accelerate the use of extensive animal studies to design therapeutic approaches for pediatric patients with lung disease. It’s become an important means to understand the differences between animal models and human systems, thereby extending studies on human lung development and diseases. 

According to Dr. Al Alam, novel in vitro culture systems that model human lung development and diseases are on the rise. Two-dimensional tissue and cell culture, as well as 3-D organoids cultures, have been the go-to models for studying human lung development and diseases. Both systems allow for manipulating gene expression and cell labeling to model disease and study specific genes or cell-cell interactions and tissue remodeling. 

“Attendees will hear about the latest advances in human lung biology. Importantly, the audience will appreciate the differences between animal models and human systems, hence the urgent need to further develop human studies,” Dr. Al Alam says. 

She adds that the knowledge gained from the novel systems used to model human lung development could be applicable to different studies of development, homeostasis, and disease, which aim to better understand the cellular and molecular pathways important in human lung development/disease. 

“We hope that attendees will use this knowledge to help accelerate the translational potential of their studies,” Dr. Al Alam says. “Our goal is to encourage and bring together new collaborations between clinicians and basic scientists to accelerate the studies on human lung development.”