Genetically engineered distal airway stem cell transplantation protects mice from pulmonary infection
Abstract 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...
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| Format: | Article |
| Language: | English |
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Springer Nature
2019-11-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201810233 |
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| author | Yue‐qing Zhou Yun Shi Ling Yang Yu‐fen Sun Yu‐fei Han Zi‐xian Zhao Yu‐jia Wang Ying Liu Yu Ma Ting Zhang Tao Ren Tina P Dale Nicholas R Forsyth Fa‐guang Jin Jie‐ming Qu Wei Zuo Jin‐fu Xu |
| author_facet | Yue‐qing Zhou Yun Shi Ling Yang Yu‐fen Sun Yu‐fei Han Zi‐xian Zhao Yu‐jia Wang Ying Liu Yu Ma Ting Zhang Tao Ren Tina P Dale Nicholas R Forsyth Fa‐guang Jin Jie‐ming Qu Wei Zuo Jin‐fu Xu |
| author_sort | Yue‐qing Zhou |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-3ebe6e243af54e25b9c58a499c7dea52 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2019-11-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-3ebe6e243af54e25b9c58a499c7dea522025-08-20T04:03:01ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842019-11-0112111610.15252/emmm.201810233Genetically engineered distal airway stem cell transplantation protects mice from pulmonary infectionYue‐qing Zhou0Yun Shi1Ling Yang2Yu‐fen Sun3Yu‐fei Han4Zi‐xian Zhao5Yu‐jia Wang6Ying Liu7Yu Ma8Ting Zhang9Tao Ren10Tina P Dale11Nicholas R Forsyth12Fa‐guang Jin13Jie‐ming Qu14Wei Zuo15Jin‐fu Xu16Department of Respiratory and Critical Care Medicine, Clinical Translation Research Center, Shanghai Pulmonary Hospital, Tongji University School of MedicineShanghai East Hospital, Tongji University School of MedicineDepartment of Respiratory and Critical Care Medicine, Clinical Translation Research Center, Shanghai Pulmonary Hospital, Tongji University School of MedicineDepartment of Respiratory and Critical Care Medicine, Clinical Translation Research Center, Shanghai Pulmonary Hospital, Tongji University School of MedicineDepartment of Respiratory and Critical Care Medicine, Clinical Translation Research Center, Shanghai Pulmonary Hospital, Tongji University School of MedicineDepartment of Respiratory and Critical Care Medicine, Clinical Translation Research Center, Shanghai Pulmonary Hospital, Tongji University School of MedicineDepartment of Respiratory and Critical Care Medicine, Clinical Translation Research Center, Shanghai Pulmonary Hospital, Tongji University School of MedicineShanghai East Hospital, Tongji University School of MedicineShanghai East Hospital, Tongji University School of MedicineRegend Therapeutics Co. LtdShanghai East Hospital, Tongji University School of MedicineGuy Hilton Research Center, School of Pharmacy and Bioengineering, Keele UniversityGuy Hilton Research Center, School of Pharmacy and Bioengineering, Keele UniversityDepartment of Respiratory and Critical Care Medicine, Tangdu Hospital, Fourth Military Medical University of PLARuijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Respiratory and Critical Care Medicine, Clinical Translation Research Center, Shanghai Pulmonary Hospital, Tongji University School of MedicineDepartment of Respiratory and Critical Care Medicine, Clinical Translation Research Center, Shanghai Pulmonary Hospital, Tongji University School of MedicineAbstract 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.https://doi.org/10.15252/emmm.201810233antimicrobial peptidedistal airway stem cellspulmonary infectiontransplantation |
| spellingShingle | Yue‐qing Zhou Yun Shi Ling Yang Yu‐fen Sun Yu‐fei Han Zi‐xian Zhao Yu‐jia Wang Ying Liu Yu Ma Ting Zhang Tao Ren Tina P Dale Nicholas R Forsyth Fa‐guang Jin Jie‐ming Qu Wei Zuo Jin‐fu Xu Genetically engineered distal airway stem cell transplantation protects mice from pulmonary infection EMBO Molecular Medicine antimicrobial peptide distal airway stem cells pulmonary infection transplantation |
| title | Genetically engineered distal airway stem cell transplantation protects mice from pulmonary infection |
| title_full | Genetically engineered distal airway stem cell transplantation protects mice from pulmonary infection |
| title_fullStr | Genetically engineered distal airway stem cell transplantation protects mice from pulmonary infection |
| title_full_unstemmed | Genetically engineered distal airway stem cell transplantation protects mice from pulmonary infection |
| title_short | Genetically engineered distal airway stem cell transplantation protects mice from pulmonary infection |
| title_sort | genetically engineered distal airway stem cell transplantation protects mice from pulmonary infection |
| topic | antimicrobial peptide distal airway stem cells pulmonary infection transplantation |
| url | https://doi.org/10.15252/emmm.201810233 |
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