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  1. AU="Xiong, Linjie"
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  1. Article ; Online: Airway Basal Stem Cells in COVID-19 Exhibit a Proinflammatory Signature and Impaired Mucocililary Differentiation.

    Bankoti, Kamakshi / Wang, Wei / Amonkar, Gaurang M / Xiong, Linjie / Shui, Jessica E / Zhao, Caiqi / Van, Eric / Mwase, Chimwemwe / Park, Jin-Ah / Mou, Hongmei / Fang, Yinshan / Que, Jianwen / Bai, Yan / Lerou, Paul H / Ai, Xingbin

    American journal of respiratory cell and molecular biology

    2024  Volume 70, Issue 1, Page(s) 26–38

    Abstract: Airway basal stem cells (BSCs) play a critical role in epithelial regeneration. Whether coronavirus disease (COVID-19) affects BSC function is unknown. Here, we derived BSC lines from patients with COVID-19 using tracheal aspirates (TAs) to circumvent ... ...

    Abstract Airway basal stem cells (BSCs) play a critical role in epithelial regeneration. Whether coronavirus disease (COVID-19) affects BSC function is unknown. Here, we derived BSC lines from patients with COVID-19 using tracheal aspirates (TAs) to circumvent the biosafety concerns of live-cell derivation. We show that BSCs derived from the TAs of control patients are
    MeSH term(s) Humans ; Epithelial Cells ; COVID-19 ; Stem Cells ; Cell Differentiation/physiology ; Bronchi
    Language English
    Publishing date 2024-01-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1025960-0
    ISSN 1535-4989 ; 1044-1549
    ISSN (online) 1535-4989
    ISSN 1044-1549
    DOI 10.1165/rcmb.2023-0104OC
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Notch signaling modulates MUC16 biosynthesis in an in vitro model of human corneal and conjunctival epithelial cell differentiation.

    Xiong, Linjie / Woodward, Ashley M / Argüeso, Pablo

    Investigative ophthalmology & visual science

    2011  Volume 52, Issue 8, Page(s) 5641–5646

    Abstract: Purpose: Notch proteins are a family of transmembrane receptors that coordinate binary cell fate decisions and differentiation in wet-surfaced epithelia. We sought to determine whether Notch signaling contributes to maintaining mucosal homeostasis by ... ...

    Abstract Purpose: Notch proteins are a family of transmembrane receptors that coordinate binary cell fate decisions and differentiation in wet-surfaced epithelia. We sought to determine whether Notch signaling contributes to maintaining mucosal homeostasis by modulating the biosynthesis of cell surface-associated mucins in an in vitro model of human corneal (HCLE) and conjunctival (HCjE) epithelial cell differentiation.
    Methods: HCLE and HCjE cells were grown at different stages of differentiation, representing nondifferentiated (preconfluent and confluent) and differentiated (stratified) epithelial cultures. Notch signaling was blocked with the γ-secretase inhibitor dibenzazepine (DBZ). The presence of Notch intracellular domains (Notch1 to Notch3) and mucin protein (MUC1, -4, -16) was evaluated by electrophoresis and Western blot analysis. Mucin gene expression was determined by TaqMan real-time polymerase chain reaction.
    Results: Here we demonstrate that Notch3 is highly expressed in undifferentiated and differentiated HCLE and HCjE cells, and that Notch1 and Notch2 biosynthesis is enhanced by induction of differentiation with serum-containing media. Inhibition of Notch signaling with DBZ impaired MUC16 biosynthesis in a concentration-dependent manner in undifferentiated cells at both preconfluent and confluent stages, but not in postmitotic stratified cells. In contrast to protein levels, the amount of MUC16 transcripts were not significantly reduced after DBZ treatment, suggesting that Notch regulates MUC16 posttranscriptionally. Immunoblots of DBZ-treated epithelial cells grown at different stages of differentiation revealed no differences in the levels of MUC1 and MUC4.
    Conclusions: These results indicate that MUC16 biosynthesis is posttranscriptionally regulated by Notch signaling at early stages of epithelial cell differentiation, and suggest that Notch activation contributes to maintaining a mucosal phenotype at the ocular surface.
    MeSH term(s) Amyloid Precursor Protein Secretases/antagonists & inhibitors ; CA-125 Antigen/biosynthesis ; CA-125 Antigen/genetics ; CA-125 Antigen/metabolism ; Cell Differentiation/physiology ; Cell Line, Transformed ; Cells, Cultured ; Conjunctiva/cytology ; Conjunctiva/metabolism ; Dibenzazepines/pharmacology ; Epithelium, Corneal/cytology ; Epithelium, Corneal/metabolism ; Gene Expression/drug effects ; Gene Expression/physiology ; Humans ; In Vitro Techniques ; Membrane Proteins/biosynthesis ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; RNA Processing, Post-Transcriptional/physiology ; Receptor, Notch3 ; Receptors, Notch/metabolism ; Signal Transduction/drug effects ; Signal Transduction/physiology
    Chemical Substances CA-125 Antigen ; Dibenzazepines ; MUC16 protein, human ; Membrane Proteins ; NOTCH3 protein, human ; Receptor, Notch3 ; Receptors, Notch ; Amyloid Precursor Protein Secretases (EC 3.4.-) ; dibenzazepine (J411KQJ8C2)
    Language English
    Publishing date 2011-07-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 391794-0
    ISSN 1552-5783 ; 0146-0404
    ISSN (online) 1552-5783
    ISSN 0146-0404
    DOI 10.1167/iovs.11-7196
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Rho/SMAD/mTOR triple inhibition enables long-term expansion of human neonatal tracheal aspirate-derived airway basal cell-like cells.

    Lu, Junjie / Zhu, Xiaobo / Shui, Jessica E / Xiong, Linjie / Gierahn, Todd / Zhang, Cheng / Wood, Michael / Hally, Suzanne / Love, J Christopher / Li, Hu / Crawford, Benjamin C / Mou, Hongmei / Lerou, Paul H

    Pediatric research

    2020  Volume 89, Issue 3, Page(s) 502–509

    Abstract: Background: Bronchopulmonary dysplasia remains one of the most common complications of prematurity, despite significant improvements in perinatal care. Functional modeling of human lung development and disease, like BPD, is limited by our ability to ... ...

    Abstract Background: Bronchopulmonary dysplasia remains one of the most common complications of prematurity, despite significant improvements in perinatal care. Functional modeling of human lung development and disease, like BPD, is limited by our ability to access the lung and to maintain relevant progenitor cell populations in culture.
    Methods: We supplemented Rho/SMAD signaling inhibition with mTOR inhibition to generate epithelial basal cell-like cell lines from tracheal aspirates of neonates.
    Results: Single-cell RNA-sequencing confirmed the presence of epithelial cells in tracheal aspirates obtained from intubated neonates. Using Rho/SMAD/mTOR triple signaling inhibition, neonatal tracheal aspirate-derived (nTAD) basal cell-like cells can be expanded long term and retain the ability to differentiate into pseudostratified airway epithelium.
    Conclusions: Our data demonstrate that neonatal tracheal aspirate-derived epithelial cells can provide a novel ex vivo human cellular model to study neonatal lung development and disease.
    Impact: Airway epithelial basal cell-like cell lines were derived from human neonatal tracheal aspirates. mTOR inhibition significantly extends in vitro proliferation of neonatal tracheal aspirate-derived basal cell-like cells (nTAD BCCs). nTAD BCCs can be differentiated into functional airway epithelium. nTAD BCCs provide a novel model to investigate perinatal lung development and diseases.
    MeSH term(s) Base Sequence ; Body Fluids/cytology ; Bronchopulmonary Dysplasia ; Cell Differentiation/drug effects ; Cell Division/drug effects ; Cells, Cultured ; Epithelial Cells/chemistry ; Epithelial Cells/cytology ; Epithelial Cells/drug effects ; Humans ; Infant, Newborn ; Primary Cell Culture ; Single-Cell Analysis ; Sirolimus/pharmacology ; Smad Proteins/antagonists & inhibitors ; Smad Proteins/physiology ; Stem Cells/cytology ; Stem Cells/drug effects ; Suction ; TOR Serine-Threonine Kinases/antagonists & inhibitors ; TOR Serine-Threonine Kinases/physiology ; Trachea/cytology ; rho-Associated Kinases/antagonists & inhibitors ; rho-Associated Kinases/physiology
    Chemical Substances Smad Proteins ; MTOR protein, human (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; rho-Associated Kinases (EC 2.7.11.1) ; Sirolimus (W36ZG6FT64)
    Language English
    Publishing date 2020-05-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 4411-8
    ISSN 1530-0447 ; 0031-3998
    ISSN (online) 1530-0447
    ISSN 0031-3998
    DOI 10.1038/s41390-020-0925-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Engineered composite tissue as a bioartificial limb graft

    Jank, Bernhard J / Xiong, Linjie / Moser, Philipp T / Guyette, Jacques P / Ren, Xi / Cetrulo, Curtis L / Leonard, David A / Fernandez, Leopoldo / Fagan, Shawn P / Ott, Harald C

    Biomaterials. 2015 Aug., v. 61

    2015  

    Abstract: The loss of an extremity is a disastrous injury with tremendous impact on a patient's life. Current mechanical prostheses are technically highly sophisticated, but only partially replace physiologic function and aesthetic appearance. As a biologic ... ...

    Abstract The loss of an extremity is a disastrous injury with tremendous impact on a patient's life. Current mechanical prostheses are technically highly sophisticated, but only partially replace physiologic function and aesthetic appearance. As a biologic alternative, approximately 70 patients have undergone allogeneic hand transplantation to date worldwide. While outcomes are favorable, risks and side effects of transplantation and long-term immunosuppression pose a significant ethical dilemma. An autologous, bio-artificial graft based on native extracellular matrix and patient derived cells could be produced on demand and would not require immunosuppression after transplantation. To create such a graft, we decellularized rat and primate forearms by detergent perfusion and yielded acellular scaffolds with preserved composite architecture. We then repopulated muscle and vasculature with cells of appropriate phenotypes, and matured the composite tissue in a perfusion bioreactor under electrical stimulation in vitro. After confirmation of composite tissue formation, we transplanted the resulting bio-composite grafts to confirm perfusion in vivo.
    Keywords adverse effects ; aesthetics ; arms (limbs) ; biocomposites ; bioreactors ; detergents ; electrical treatment ; ethics ; extracellular matrix ; immunosuppression ; muscles ; patients ; phenotype ; prostheses ; rats ; risk
    Language English
    Dates of publication 2015-08
    Size p. 246-256.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 603079-8
    ISSN 0142-9612
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2015.04.051
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Engineering pulmonary vasculature in decellularized rat and human lungs.

    Ren, Xi / Moser, Philipp T / Gilpin, Sarah E / Okamoto, Tatsuya / Wu, Tong / Tapias, Luis F / Mercier, Francois E / Xiong, Linjie / Ghawi, Raja / Scadden, David T / Mathisen, Douglas J / Ott, Harald C

    Nature biotechnology

    2015  Volume 33, Issue 10, Page(s) 1097–1102

    Abstract: Bioengineered lungs produced from patient-derived cells may one day provide an alternative to donor lungs for transplantation therapy. Here we report the regeneration of functional pulmonary vasculature by repopulating the vascular compartment of ... ...

    Abstract Bioengineered lungs produced from patient-derived cells may one day provide an alternative to donor lungs for transplantation therapy. Here we report the regeneration of functional pulmonary vasculature by repopulating the vascular compartment of decellularized rat and human lung scaffolds with human cells, including endothelial and perivascular cells derived from induced pluripotent stem cells. We describe improved methods for delivering cells into the lung scaffold and for maturing newly formed endothelium through co-seeding of endothelial and perivascular cells and a two-phase culture protocol. Using these methods we achieved ∼75% endothelial coverage in the rat lung scaffold relative to that of native lung. The regenerated endothelium showed reduced vascular resistance and improved barrier function over the course of in vitro culture and remained patent for 3 days after orthotopic transplantation in rats. Finally, we scaled our approach to the human lung lobe and achieved efficient cell delivery, maintenance of cell viability and establishment of perfusable vascular lumens.
    MeSH term(s) Animals ; Cell-Free System ; Cells, Cultured ; Endothelial Cells/cytology ; Endothelial Cells/physiology ; Equipment Design ; Equipment Failure Analysis ; Humans ; Lung/chemistry ; Male ; Neovascularization, Physiologic/physiology ; Pulmonary Artery/cytology ; Pulmonary Artery/growth & development ; Rats ; Rats, Sprague-Dawley ; Regeneration/physiology ; Species Specificity ; Tissue Engineering/instrumentation ; Tissue Scaffolds
    Language English
    Publishing date 2015-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1311932-1
    ISSN 1546-1696 ; 1087-0156
    ISSN (online) 1546-1696
    ISSN 1087-0156
    DOI 10.1038/nbt.3354
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Engineered composite tissue as a bioartificial limb graft.

    Jank, Bernhard J / Xiong, Linjie / Moser, Philipp T / Guyette, Jacques P / Ren, Xi / Cetrulo, Curtis L / Leonard, David A / Fernandez, Leopoldo / Fagan, Shawn P / Ott, Harald C

    Biomaterials

    2015  Volume 61, Page(s) 246–256

    Abstract: The loss of an extremity is a disastrous injury with tremendous impact on a patient's life. Current mechanical prostheses are technically highly sophisticated, but only partially replace physiologic function and aesthetic appearance. As a biologic ... ...

    Abstract The loss of an extremity is a disastrous injury with tremendous impact on a patient's life. Current mechanical prostheses are technically highly sophisticated, but only partially replace physiologic function and aesthetic appearance. As a biologic alternative, approximately 70 patients have undergone allogeneic hand transplantation to date worldwide. While outcomes are favorable, risks and side effects of transplantation and long-term immunosuppression pose a significant ethical dilemma. An autologous, bio-artificial graft based on native extracellular matrix and patient derived cells could be produced on demand and would not require immunosuppression after transplantation. To create such a graft, we decellularized rat and primate forearms by detergent perfusion and yielded acellular scaffolds with preserved composite architecture. We then repopulated muscle and vasculature with cells of appropriate phenotypes, and matured the composite tissue in a perfusion bioreactor under electrical stimulation in vitro. After confirmation of composite tissue formation, we transplanted the resulting bio-composite grafts to confirm perfusion in vivo.
    MeSH term(s) Animals ; Artificial Limbs ; Bioartificial Organs ; Cell Differentiation/physiology ; Cell-Free System ; Cells, Cultured ; Equipment Failure Analysis ; Extracellular Matrix/chemistry ; Male ; Muscle, Skeletal/cytology ; Muscle, Skeletal/growth & development ; Prosthesis Design ; Rats ; Rats, Sprague-Dawley ; Stem Cells/cytology ; Stem Cells/physiology ; Tissue Engineering/instrumentation ; Tissue Scaffolds
    Language English
    Publishing date 2015-08
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 603079-8
    ISSN 1878-5905 ; 0142-9612
    ISSN (online) 1878-5905
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2015.04.051
    Database MEDical Literature Analysis and Retrieval System OnLINE

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