Stem cells, cell therapies, and bioengineering in lung biology and disease 2021.

The 9th biennial conference titled "Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases" was hosted virtually, due to the ongoing COVID-19 pandemic, in collaboration with the University of Vermont Larner College of Medicine, the National Heart, Lung, and Blood Institute, the Alpha-1 Foundation, the Cystic Fibrosis Foundation, and the International Society for Cell & Gene Therapy. The event was held from July 12th through 15th, 2021 with a pre-conference workshop held on July 9th. As in previous years, the objectives remained to review and discuss the status of active research areas involving stem cells (SCs), cellular therapeutics, and bioengineering as they relate to the human lung. Topics included 1) technological advancements in the in situ analysis of lung tissues, 2) new insights into stem cell signaling and plasticity in lung remodeling and regeneration, 3) the impact of extracellular matrix in stem cell regulation and airway engineering in lung regeneration, 4) differentiating and delivering stem cell therapeutics to the lung, 5) regeneration in response to viral infection, and 6) ethical development of cell-based treatments for lung diseases. This selection of topics represents some of the most dynamic and current research areas in lung biology. The virtual workshop included active discussion on state-of-the-art methods relating to the core features of the 2021 conference, including in situ proteomics, lung-on-chip, induced pluripotent stem cell (iPSC)-airway differentiation, and light sheet microscopy. The conference concluded with an open discussion to suggest funding priorities and recommendations for future research directions in basic and translational lung biology.

Lung tissue bioengineering for chronic obstructive pulmonary disease: overcoming the need for lung transplantation from human donors.

Introduction: Chronic obstructive pulmonary disease (COPD) affects more than 380 million people, causing more than 3 million deaths annually worldwide. Despite this enormous burden, currently available therapies are largely limited to symptom control. Lung transplant is considered for end-stage disease but is severely limited by the availability of human organs. Furthermore, the pre-transplant course is a complex orchestration of locating and harvesting suitable lungs, and the post-transplant course is complicated by rejection and infection. Lung tissue bioengineering has the potential to relieve the organ shortage and improve the post-transplant course by generating patient-specific lungs for transplant. Additionally, emerging progenitor cell therapies may facilitate in vivo regeneration of pulmonary tissue, obviating the need for transplant. Areas Covered: We review several lung tissue bioengineering approaches including the recellularization of decellularized scaffolds, 3D bioprinting, genetically-engineered xenotransplantation, blastocyst complementation, and direct therapy with progenitor cells. Articles were identified by searching relevant terms (see Key Words) in the PubMed database and selected for inclusion based on novelty and uniqueness of their approach. Expert Opinion: Lung tissue bioengineering research is in the early stages. Of the methods reviewed, only direct cell therapy has been investigated in humans. We anticipate a minimum of 5-10 years before human therapy will be feasible.

Decellularization of Intact Lung Tissue Through Vasculature and Airways Using Negative and Positive Pressure.

Decellularization allows the production of extracellular matrix (ECM) scaffolds. Here we describe the use of combined positive pressure and negative pressure to drive decellularization reagents into the vasculature and airways, respectively, of structurally intact lungs in order to remove cells and cellular material leaving an intact ECM scaffold.