Genetically engineered distal airway stem cell transplantation protects mice from pulmonary infection

Dale, Tina; Forsyth, Nick

Abstract

Severe pulmonary infection is a major threat to human health accompanied by substantial, which increases medical costs, prolonged inpatient requirements, and high mortality rates. New anti-microbial therapeutic strategies are urgently required to address with the emergence of antibiotic resistance and persistent bacterial infections. In this study, we show that constitutive expression of a native anti-microbial peptide hCAP-18/LL-37 (LL9 37) in transgenic mice aids in clearing Pseudomonas aeruginosa (PAO1), a major pathogen of clinical pulmonary infection. Orthotopic transplantation of adult mouse distal airway stem cells (DASCs), genetically engineered to express LL-37, into injured mouse lung foci enabled large scale incorporation of cells and long-term release of the host defense peptide, protecting the mice from bacterial pneumonia and hypoxemia. Further, adult human DASCs were isolated, expanded, and genetically engineered to demonstrate successful construction of an anti-infective artificial lung. Together, our stem cell-based gene delivery therapeutic platform proposes a new strategy for addressing recurrent pulmonary infections with, providing future translational opportunities.

Citation

Dale, T., & Forsyth, N. (2020). Genetically engineered distal airway stem cell transplantation protects mice from pulmonary infection. EMBO Molecular Medicine, https://doi.org/10.15252/emmm.201810233

• Acceptance Date: Nov 4, 2019
• Publication Date: Jan 9, 2020
• Journal: EMBO Molecular Medicine
• Print ISSN: 1757-4676
• Publisher: Wiley
• DOI: https://doi.org/10.15252/emmm.201810233
• Keywords: anti-microbial peptide; distal airway stem cells; pulmonary infection; transplantation
• Publisher URL: http://doi.org/10.15252/emmm.201810233