Future Directions in Stem Cells, Cell Therapy, and Bioengineering in Lung Biology and Diseases.

Abstract

Over the past two decades, progress in stem cell biology, bioengineering, and systems biology has improved our understanding of lung regeneration and repair. Building on work presented at the 20th Anniversary Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases Conference, this review examines the evolving trajectory of the field and outlines remaining challenges and opportunities for future research. We focus on three main areas: improving ex vivo lung models to better capture cellular heterogeneity and biomechanics; using single-cell, spatial, and computational approaches to support translation into clinical practice; and innovative therapeutic strategies, including gene therapies, epithelial cell therapies, immune cell engineering, extracellular matrix reconditioning, senescence targeting, and whole-organ bioengineering and xenotransplantation. Together, these approaches are shifting lung regeneration from descriptive studies toward precision, mechanism-driven therapies. Future progress in lung regenerative medicine will require integration of omics-driven insights with functional validation and biomaterial innovation to achieve meaningful clinical impact.