Genetically engineered distal airway stem cell transplantation protects mice from pulmonary infection
Open accessAbstract
Severe pulmonary infection is a major threat to human health accompanied by substantial medical costs, prolonged inpatient requirements, and high mortality rates. New antimicrobial therapeutic strategies are urgently required to address the emergence of antibiotic resistance and persistent bacterial infections. In this study, we show that the constitutive expression of a native antimicrobial peptide LL‐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, correlates of DASCs in adult humans 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 future translational opportunities.
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The antibacterial peptide LL-37 from humans has broad-spectrum antibacterial activity by increasing the membrane permeability of bacteria, neutralizing endotoxins, and suppressing the production of proinflammatory factors.
“The antibacterial peptide LL-37 from humans was found to have broad-spectrum antibacterial activity31–34 by increasing the membrane permeability of bacteria, neutralizing endotoxins, and suppressing the production of proinflammatory factors.35”
From Identification of heptapeptides targeting a lethal bacterial strain in septic mice through an integrative approach (2022) · cites this paper as [32]
The Introduction says human LL-37 has broad bactericidal activity against Gram-negative and Gram-positive bacteria. The Results report lower IL-6 and IL-1β mRNA in infected LL-37 transgenic mouse lungs, but do not establish that LL-37 directly suppresses their production. Neither the Introduction nor the retrieved Results and Discussion passages establish increased bacterial membrane permeability or endotoxin neutralization as mechanisms. (LLM, conf=0.86)
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- Authors
- Zhou, Y., Shi, Y., Yang, L., Sun, Y., Han, Y., Zhao, Z., Wang, Y., Liu, Y., Ma, Y., Zhang, T., Ren, T., Dale, T. P., Forsyth, N. R., Jin, F., Qu, J., Zuo, W., & Xu, J.
- Affiliations
- Tongji University (CN)
- Regend Therapeutics (China) (CN)
- Keele University (GB)
- Corresponding author
- Zuo, Wei
- Xu, Jin‐fu
- ORCID
- Venue
- EMBO Molecular Medicine
- Published
- 2019-11-29
- Volume
- 12
- Issue
- 1
- Pages
- e10233-e10233
- ISSN
- 1757-4676 (ISSN-L)
- 1757-4684
- PMC
- PMC6949487
- OpenAlex
- W2990637450
- Cited by
- 37
- References
- 48
- Citations by year
- 2025: 7 · 2024: 7 · 2023: 8 · 2022: 7 · 2021: 4 · 2020: 3 · 2019: 1
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- EMBO Molecular Medicine (publishedVersion, cc-by-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Keele Research Repository (Keele University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Key Research Program (2017YFA0104600)
- The National Science Fund for Distinguished Young Scholars (81925001)
- Shanghai Leading Talent Program (2016036)
- Key Project of Fundamental Research Funds for the Central Universities (2017ZD002)
- Project of the Shanghai Hospital Development Center (16CR3036A)
- Youth 1000 Talent Plan of China
- Tongji University Basic Scientific Research‐Interdisciplinary Fund and 985 Grant
- Shanghai Pulmonary Hospital Annual Grant
- National Science Foundation of China (81770073, NSFC81630001, 81670006, 81570091, 81600003)
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- LL-37, antimicrobial peptides, Pseudomonas aeruginosa, bacterial pneumonia, stem cell transplantation, transgenic mice, gene delivery, artificial lung, hypoxemia, lung injury, antibiotic resistance, pulmonary infection
- MeSH terms
- Animals, Escherichia coli, Female, Lung Diseases, Male, Mice, Inbred C57BL, Mice, Transgenic, Pseudomonas aeruginosa, Pseudomonas Infections, Rats, Sprague-Dawley, Antimicrobial Cationic Peptides, Stem Cell Transplantation, Mice, Rats, Cathelicidins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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