Airway Reconstruction via Stem Cell-Based Therapy
Abstract
Airway damage in the combat zone is among the leading causes of potentially preventable combat death. While the reasons for the high degree of tissue loss and destruction are multifactorial, i.e., improvised explosive devices and toxic gas exposure, the consequences could be devastating and lethal. Airway management is thus critical in the resuscitation of the severely injured trauma patients. The management of upper airway/tracheal defects is a challenging and evolving field in combat zone and civilian world. For severe long-segment tracheal damages, no effective treatment is available. Tracheal transplantation and tracheal/airway regeneration may benefit greatly these patients. A clinically relevant tracheal substitute must be readily available, durable, and foremost safe. Unfortunately, such a substitute has remained elusive. With these challenges in mind, we aim to tackle the problem by building a bioengineered tracheal/airway graft from human pluripotent stem cells (hPSCs). Pluripotent stem cells are “master” cells, which can potentially produce any cell or tissue the body needs to repair itself. Like all stem cells, pluripotent stem cells are also able to self-renew, meaning they can perpetually create more copies of themselves. Thus, stem cell-based therapy can provide a theoretically unlimited source of cells for regenerative medicine. Our lab has previously developed a novel method to expand basal cells, the stem cell of the airways, from hPSCs. These basal cells can give rise to mature cells in the airway and grow on mouse trachea, strongly supporting their regenerative potential ex vivo. To take this further, we will transplant the basal cells into the damaged trachea in mice. We will determine if these cells are able to multiply, promoting growth and most importantly, safely repair the damaged tissue. We will establish an optimal method to better fuse these cells to the host tissues, maximizing their regenerative capacity. Many attempts to replace the trachea with synthetic scaffolds have failed in the past. Tissues-engineered techniques have shown the greatest promise but are hugely limited by the insufficient number of cells we can use. Our work will rely on the use of stem cells, which provide a potentially unlimited source of cells. Our result has enormous potential for clinical application for repairing severe damaged airway. This could represent a potential huge leap forward for airway reconstruction and using hPSCs for developing future personalized stem cell therapies to improve respiratory health.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110081
Entities
People
- Ya-Wen Chen
Organizations
- United States Army
- University of Southern California