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

Zhou, Yueqing; Shi, Yun; Yang, Ling; Sun, Yufen; Han, Yufei; Zhao, Zhongyang; Wang, Yu‐jia; Liu, Ying; Ma, Yu; Zhang, Ting; Ren, Tao; Dale, Tina P; Forsyth, Nicholas R.; Jin, Fang; Jian, Qu; Zuo, Wei; Xu, Jin‐Fu

doi:10.15252/emmm.201810233

Cited by 26 publications

(23 citation statements)

References 44 publications

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“…ALI cultures and organoids derived from primary cells or iPSC maintain the patient's genetic, functional and phenotypic signatures in vitro, allowing for accurate prediction of drug responses of individual patients (Gras et al, 2012;Bartfeld and Clevers, 2017;Oost et al, 2018;Kim et al, 2019;Leibel et al, 2019). In combination with genetic modification tools, such as lentiviruses or CRISPR/Cas9, organoids, and ALI cultures can be used to study the effects of specific genetic mutations in various diseases and identify potential drug targets and cell therapies (Schwank et al, 2013;Zhou et al, 2019). In addition, ALI and organoids can be expanded from small amounts of starting materials, and can be maintained over a long period of time to provide enough samples for a wide variety of laboratory analysis, such as efficacy, toxicology, multi-omics analyses (such as RNA-Seq, proteomic, and metabolomic).…”

Section: Resultsmentioning

confidence: 99%

“…Two of the potential limitations in the use of HDPs as antiinfection or anti-inflammatory therapy are peptide instability and off-target toxicity (Johansson et al, 1998;Sieprawska-Lupa et al, 2004;Heilborn et al, 2005;Vandamme et al, 2012;Mishra et al, 2017;Zhou et al, 2019). To address these concerns, Zhou and colleagues proposed to use stem cell-based gene delivery therapy with the human HDP LL-37 to provide local protection against pulmonary infections (Zhou et al, 2019). The HDP peptide LL-37 is known to have a broad range of antimicrobial and immunomodulatory activities that provides protection against infections (Vandamme et al, 2012;van der Does et al, 2012).…”

Section: Induced Pluripotent Stem Cells-derived Immune Cellsmentioning

confidence: 99%

“…The HDP peptide LL-37 is known to have a broad range of antimicrobial and immunomodulatory activities that provides protection against infections (Vandamme et al, 2012;van der Does et al, 2012). A transgenic mouse strain was constructed that constitutively expressed LL-37 (LL-37 +/+ ) to confirm the in vivo protective effects of the peptide against P. aeruginosa PA01 infection (Zhou et al, 2019). Using RNA-Seq, they compared the transcriptomic profiles of wild-type and LL-37 +/+ mice before and after PA01 infection (Figure 2).…”

Section: Induced Pluripotent Stem Cells-derived Immune Cellsmentioning

confidence: 99%

“…The regenerated LL-37 lung, containing LL-37-mDASC, enhanced bacterial clearance after intratracheal challenge with either PA01 or E. coli. By using a combination of genetically engineered stem cells, animal and organoid models and RNA-Seq analyses, Zhou and colleagues showed that genetically engineered DASCs, which constitutively express the human HDP LL-37, can provide protection against pulmonary infections and enhance the repair of lung injury (Zhou et al, 2019).…”

Section: Induced Pluripotent Stem Cells-derived Immune Cellsmentioning

confidence: 99%

“…*P < 0.05; **P < 0.01; ****P < 0.0001. These results were from Zhou et al (2019), published under the terms of the CC by 4.0 license. Full terms at https:// creativecommons.org/licenses/by/4.0/.…”

Section: Lung Modelsmentioning

confidence: 99%

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Utilizing Organoid and Air-Liquid Interface Models as a Screening Method in the Development of New Host Defense Peptides

Choi

Lee

et al. 2020

Front. Cell. Infect. Microbiol.

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Host defense peptides (HDPs), also known as antimicrobial peptides, are naturally occurring polypeptides (∼12-50 residues) composed of cationic and hydrophobic amino acids that adopt an amphipathic conformation upon folding usually after contact with membranes. HDPs have a variety of biological activities including immunomodulatory, anti-inflammatory, anti-bacterial, and anti-biofilm functions. Although HDPs have the potential to address the global threat of antibiotic resistance and to treat immune and inflammatory disorders, they have yet to achieve this promise. Indeed, there are several challenges associated with bringing peptide-based drug candidates from the lab bench to clinical practice, including identifying appropriate indications, stability, toxicity, and cost. These challenges can be addressed in part by the development of innate defense regulator (IDR) peptides and peptidomimetics, which are synthetic derivatives of HDPs with similar or better efficacy, increased stability, and reduced toxicity and cost of the original HDP. However, one of the largest gaps between basic research and clinical application is the validity and translatability of conventional model systems, such as cell lines and animal models, for screening HDPs and their derivatives as potential drug therapies. Indeed, such translation has often relied on animal models, which have only limited validity. Here we discuss the recent development of human organoids for disease modeling and drug screening, assisted by the use of omics analyses. Organoids, developed from primary cells, cell lines, or human pluripotent stem cells, are three-dimensional, self-organizing structures that closely resemble their corresponding in vivo organs with regards to immune responses, tissue organization, and physiological properties; thus, organoids represent a reliable method for studying efficacy, formulation, toxicity and to some extent drug stability and pharmacodynamics. The use of patient-derived organoids enables the study of patient-specific efficacy, toxicogenomics and drug response predictions. We outline how organoids and omics data analysis can be leveraged to aid in the clinical translation of IDR peptides.

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Section: Resultsmentioning

confidence: 99%

Section: Induced Pluripotent Stem Cells-derived Immune Cellsmentioning

confidence: 99%

Section: Induced Pluripotent Stem Cells-derived Immune Cellsmentioning

confidence: 99%

Section: Induced Pluripotent Stem Cells-derived Immune Cellsmentioning

confidence: 99%

Section: Lung Modelsmentioning

confidence: 99%

See 3 more Smart Citations

Utilizing Organoid and Air-Liquid Interface Models as a Screening Method in the Development of New Host Defense Peptides

Choi

Lee

et al. 2020

Front. Cell. Infect. Microbiol.

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The Development of Lung Tissue Engineering: From Biomaterials to Multicellular Systems

Ma,

Wu,

2024

Adv Healthcare Materials

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The challenge of the treatment of end‐stage lung disease poses an urgent clinical demand for lung tissue engineering. Over the past few years, various lung tissue‐engineered constructs are developed for lung tissue regeneration and respiratory pathology study. In this review, an overview of recent achievements in the field of lung tissue engineering is proposed. The introduction of lung structure and lung injury are stated briefly at first. After that, the lung tissue‐engineered constructs are categorized into three types: acellular, monocellular, and multicellular systems. The different bioengineered constructs included in each system that can be applied to the reconstruction of the trachea, airway epithelium, alveoli, and even whole lung are described in detail, followed by the highlight of relevant representative research. Finally, the challenges and future directions of biomaterials, manufacturing technologies, and cells involved in lung tissue engineering are discussed. Overall, this review can provide referable ideas for the realization of functional lung regeneration and permanent lung substitution.

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Pulmonary endogenous progenitor stem cell subpopulation: Physiology, pathogenesis, and progress

Liu

Jiang

et al. 2023

Journal of Intensive Medicine

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

Cited by 26 publications

References 44 publications

Utilizing Organoid and Air-Liquid Interface Models as a Screening Method in the Development of New Host Defense Peptides

Utilizing Organoid and Air-Liquid Interface Models as a Screening Method in the Development of New Host Defense Peptides

The Development of Lung Tissue Engineering: From Biomaterials to Multicellular Systems

Pulmonary endogenous progenitor stem cell subpopulation: Physiology, pathogenesis, and progress

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