scholarly journals Stable Long-Term Culture of Human Distal Airway Stem Cells for Transplantation

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yueqing Zhou ◽  
Yujia Wang ◽  
Dandan Li ◽  
Ting Zhang ◽  
Yu Ma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Lung Model ◽  
Mouse Lung ◽  
Secretory Cells ◽  
Type I ◽  
Alveolar Cells ◽  
Epithelial Regeneration ◽  
Distal Airway ◽  
Promising Therapeutic Approach

There is a population of p63+/Krt5+ distal airway stem cells (DASCs) quiescently located in the airway basal epithelium of mammals, responding to injury and airway epithelial regeneration. They hold the ability to differentiate into multiple pulmonary cell types and can repopulate the epithelium after damage. The current study aims at gaining further insights into the behavior and characteristics of the DASCs isolated from the patient lung and exploring their clinical translational potential. Human DASCs were brushed off through the bronchoscopic procedure and expanded under the pharmaceutical-grade condition. Their phenotype stability in long-term cell culture was analyzed, followed by safety evaluation and tumorigenic analysis using multiple animal models including rodents and nonhuman primate. The chimerism of the human-mouse lung model indicated that DASC pedigrees could give rise to multiple epithelial types, including type I alveolar cells as well as bronchiolar secretory cells, to regenerate the distal lung. Taken together, the results suggested that DASC transplantation could be a promising therapeutic approach for unmet needs in respiratory medicine including the COVID-19-related diseases.

scholarly journals Intestinal epithelial cell-specific IGF1 promotes the expansion of intestinal stem cells during epithelial regeneration and functions on the intestinal immune homeostasis

2018 ◽  
Vol 315 (4) ◽  
pp. E638-E649 ◽  
Author(s):  
Yu Zheng ◽  
Yongli Song ◽  
Qi Han ◽  
Wenjie Liu ◽  
Jiuzhi Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial Cell ◽  
Intestinal Epithelial Cell ◽  
High Throughput Sequencing ◽  
Secretory Cells ◽  
Intestinal Epithelial ◽  
Epithelial Stem Cells ◽  
Microbial Composition ◽  
Epithelial Regeneration

It is well known that insulin-like growth factor 1 (IGF1) acts as a trophic factor in small intestine under both physiological and pathophysiological conditions. However, it still lacks direct in vivo evidence of the functions of intestinal epithelial cell (IEC)-specific IGF1 under both normal and pathological conditions. Using IEC-specific IGF1-knockout (cKO) mice and Lgr5-eGFP-CreERT mice, we demonstrate that IEC-specific IGF1 can enhance nutrient uptake, reduce protein catabolism and energy consumption, and promote the proliferation and expansion of intestinal epithelial cells, including intestinal epithelial stem cells and intestinal secretory cells. Next, we showed that IEC-specific IGF1 renders IECs resistant to irradiation and promotes epithelial regeneration. Strikingly, transcriptome profiling assay revealed that many differentially expressed genes involved in the differentiation and maturation of lymphoid lineages were significantly suppressed in the cKO mice as compared with the control mice. We demonstrated that deletion of IGF1 in IECs enhances bacterial translocation to the mesenteric lymph nodes and liver. Furthermore, high-throughput sequencing of 16S ribosomal RNA genes of gut microbiota revealed that IEC-specific IGF1 loss profoundly affected the gut microbial composition at various levels of classification. Therefore, our findings shed light on the in vivo roles of IEC-specific IGF1 in intestinal homeostasis, epithelial regeneration, and immunity, broadening our current insights on IGF1 functions.

scholarly journals Radiation Induces Pulmonary Fibrosis by Promoting the Fibrogenic Differentiation of Alveolar Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Lu-Kai Wang ◽  
Tsai-Jung Wu ◽  
Ji-Hong Hong ◽  
Fang-Hsin Chen ◽  
John Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Tissue Growth ◽  
Alveolar Epithelial Cells ◽  
Type I ◽  
Alveolar Cells ◽  
Mesenchymal Transition ◽  
Alveolar Epithelial ◽  
Radiation Induced

The lung is a radiosensitive organ, which imposes limits on the therapeutic dose in thoracic radiotherapy. Irradiated alveolar epithelial cells promote radiation-related pneumonitis and fibrosis. However, the role of lung stem cells (LSCs) in the development of radiation-induced lung injury is still unclear. In this study, we found that both LSCs and LSC-derived type II alveolar epithelial cells (AECII) can repair radiation-induced DNA double-strand breaks, but the irradiated LSCs underwent growth arrest and cell differentiation faster than the irradiated AECII cells. Moreover, radiation drove LSCs to fibrosis as shown with the elevated levels of markers for epithelial-mesenchymal transition and myofibroblast (α-smooth muscle actin (α-SMA)) differentiation in in vitro and ex vivo studies. Increased gene expressions of connective tissue growth factor and α-SMA were found in both irradiated LSCs and alveolar cells, suggesting that radiation could induce the fibrogenic differentiation of LSCs. Irradiated LSCs showed an increase in the expression of surfactant protein C (SP-C), the AECII cell marker, and α-SMA, and irradiated AECII cells expressed SP-C and α-SMA. These results indicated that radiation induced LSCs to differentiate into myofibroblasts and AECII cells; then, AECII cells differentiated further into either myofibroblasts or type I alveolar epithelial cells (AECI). In conclusion, our results revealed that LSCs are sensitive to radiation-induced cell damage and may be involved in radiation-induced lung fibrosis.

Long-term, feeder-free maintenance of human embryonic stem cells by mussel-inspired adhesive heparin and collagen type I

2016 ◽  
Vol 32 ◽  
pp. 138-148 ◽  
Author(s):  
Mihyun Lee ◽  
Youngjin Kim ◽  
Ji Hyun Ryu ◽  
Kyuri Kim ◽  
Yong-Mahn Han ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Collagen Type ◽  
Embryonic Stem ◽  
Collagen Type I ◽  
Type I

scholarly journals Simultaneous isolation of endothelial and alveolar epithelial type I and type II cells during mouse lung development in the absence of a transgenic reporter

2020 ◽  
Vol 318 (4) ◽  
pp. L619-L630 ◽  
Author(s):  
Yves Donati ◽  
Sanja Blaskovic ◽  
Isabelle Ruchonnet-Métrailler ◽  
Josefina Lascano Maillard ◽  
Constance Barazzone-Argiroffo
Keyword(s):  
Epithelial Cell ◽  
De Novo ◽  
Morphological Changes ◽  
Alveolar Epithelial Cell ◽  
Mouse Lung ◽  
Cell Populations ◽  
Type I ◽  
Type Ii ◽  
Alveolar Cells ◽  
Alveolar Epithelial

Mouse lung developmental maturation and final alveolarization phase begin at birth. During this dynamic process, alveolar cells modify their morphology and anchorage to the extracellular matrix. In particular, alveolar epithelial cell (AEC) type I undergo cytoplasmic flattening and folding to ensure alveoli lining. We developed FACS conditions for simultaneous isolation of alveolar epithelial and endothelial cells in the absence of specific reporters during the early and middle alveolar phase. We evidenced for the first time a pool of extractable epithelial cell populations expressing high levels of podoplanin at postnatal day (pnd)2, and we confirmed by RT-qPCR that these cells are already differentiated but still immature AEC type I. Maturation causes a decrease in isolation yields, reflecting the morphological changes that these cell populations are undergoing. Moreover, we find that major histocompatibility complex II (MHCII), reported as a good marker of AEC type II, is poorly expressed at pnd2 but highly present at pnd8. Combined experiments using LysoTracker and MHCII demonstrate the de novo acquisition of MCHII in AEC type II during lung alveolarization. The lung endothelial populations exhibit FACS signatures from vascular and lymphatic compartments. They can be concomitantly followed throughout alveolar development and were obtained with a noticeable increased yield at the last studied time point (pnd16). Our results provide new insights into early lung alveolar cell isolation feasibility and represent a valuable tool for pure AEC type I preparation as well as further in vitro two- and three-dimensional studies.

scholarly journals Long-term evolution of mucopolysaccharidosis type I in twins treated with enzyme replacement therapy plus hematopoietic stem cells transplantation

Heliyon ◽  
2021 ◽  
pp. e07740
Author(s):  
Luis M. Carbajal-Rodríguez ◽  
Martín Pérez-García ◽  
Raymundo Rodríguez-Herrera ◽  
Haydeé Salazar Rosales ◽  
Alberto Olaya-Vargas
Keyword(s):  
Stem Cells ◽  
Type I ◽  
Mucopolysaccharidosis Type ◽  
Mucopolysaccharidosis Type I ◽  
Hematopoietic Stem ◽  
Enzyme Replacement ◽  
Term Evolution ◽  
Stem Cells Transplantation ◽  
Hematopoietic Stem Cells Transplantation

scholarly journals Gfi1-expressing Paneth cells revert to stem cells following intestinal injury

2018 ◽  
Author(s):  
Min-Shan Chen ◽  
Yuan-Hung Lo ◽  
Joann Butkus ◽  
Winnie Zou ◽  
Yu-Jung Tseng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Intestinal Epithelium ◽  
Goblet Cells ◽  
Intestinal Injury ◽  
Model Systems ◽  
Treatment Modalities ◽  
Secretory Cells ◽  
Chemotherapy Drugs ◽  
Normal Tissues ◽  
Epithelial Regeneration

AbstractBackground＆AimChemotherapy drugs harm rapidly dividing normal healthy cells such as those lining the gastrointestinal tract, causing morbidity and mortality that complicates medical treatment modalities. Growth Factor-Independent 1 (GFI1) is a zinc finger transcriptional repressor implicated in the differentiation of secretory precursors into Paneth and goblet cells in the intestinal epithelium. We hypothesize that stimulating the reversion of Gfi1+ secretory cells into stem cells will improve intestinal epithelial regeneration and mitigate injury.MethodsGfi1 reporter mice (Gfi1cre/+; ROSA26 LSL-YFP) were treated with Doxorubicin, radiation, anti-CD3 antibody, and rotavirus to induce intestinal injury. Mice and intestinal organoids (enteroids) were used to investigate cellular repair mechanisms following injury.ResultsUnder homeostatic conditions, Gfi1-lineage cells are Paneth and goblet cells, which were non-proliferative and not part of the stem cell pool. After injury, Gfi1+ secretory cells can re-enter the cell cycle and give rise to all cell lineages of the intestinal epithelium including stem cells. Reversion of Gfi1-lineage cells was observed in other injury model systems, including irradiation and anti-CD3 treatment, but not in ISC-sparing rotavirus infection. Our results also demonstrated that PI3kinase/AKT activation improved cell survival, and elevated WNT signaling increased the efficiency of Gfi1+ cell reversion upon injury.ConclusionsThese findings indicate that Gfi1+ secretory cells display plasticity and reacquire stemness following severe damage. Moreover, PI3kinase/AKT and WNT are key regulators involved in injury-induced regeneration. Our studies identified potential therapeutic intervention strategies to mitigate the adverse effects of chemotherapy-induced damage to normal tissues and improve the overall effectiveness of cancer chemotherapy.

scholarly journals Gene Profiles in a Smoke-Induced COPD Mouse Lung Model Following Treatment with Mesenchymal Stem Cells

2016 ◽  
Vol 39 (10) ◽  
pp. 728-733 ◽  
Author(s):  
You-Sun Kim ◽  
Nurdan Kokturk ◽  
Ji-Young Kim ◽  
Sei Won Lee ◽  
Jaeyun Lim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Lung Model ◽  
Mouse Lung ◽  
Model Following ◽  
Gene Profiles

scholarly journals The Normal and Fibrotic Mouse Lung in Situ Classified by High Dimensional Single Cell Analysis on Routinely Processed Tissue

2021 ◽  
Author(s):  
Roberta Ciccimarra ◽  
Maddalena M. Bolognesi ◽  
Matteo Zoboli ◽  
Giorgio Cattoretti ◽  
Fabio F. Stellari ◽  
...  
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Progressive Increase ◽  
Mouse Lung ◽  
Alveolar Type ◽  
Type I ◽  
Alveolar Cells ◽  
Antibody Staining ◽  
Fibrotic Process

Abstract Single cell classification is elucidating homeostasis and pathology in tissues and whole organs. We applied in situ spatial proteomics by multiplex antibody staining to routinely processed mouse lung, healthy and during a fibrosis model. With a limited validated antibody panel (24) we classify the normal constituents (alveolar type I and II, bronchial epithelia, endothelial, muscular, stromal and hematopoietic cells) and by quantitative measurements, we show the progress of lung fibrosis over a 4 weeks course, the changing landscape and the cell-specific quantitative variation of a multidrug transporter. An early decline in AT2 alveolar cells and a progressive increase in stromal cells seems at the core of the fibrotic process.

scholarly journals Re-entry into mitosis and regeneration of intestinal stem cells through enteroblast dedifferentiation in Drosophila midguts

2021 ◽  
Author(s):  
Aiguo Tian ◽  
Virginia Morejon ◽  
Sarah Kohoutek ◽  
Yi-Chun Huang ◽  
Wu-Min Deng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pathogenic Bacteria ◽  
Growth Factor Receptor ◽  
Lineage Tracing ◽  
Intestinal Stem Cells ◽  
Stem Cell Marker ◽  
Secretory Cells ◽  
Ras Signaling ◽  
Epithelial Regeneration ◽  
Resident Stem Cells

Many adult tissues and organs including the intestine rely on resident stem cells to maintain homeostasis. In mammalian intestines, upon ablation of resident stem cells, the progenies of intestinal stem cells (ISCs) such as secretory cells and tuft cells can dedifferentiate to generate ISCs to drive epithelial regeneration, but whether and how the ISC progenies dedifferentiate to generate ISCs under physiological conditions remains unknown. Here we show that infection of pathogenic bacteria induces enteroblasts (EBs) as one type of ISC progenies to re-enter the mitotic cycle in the Drosophila intestine. The re-entry into mitosis is dependent on epithermal growth factor receptor (EGFR)-Ras signaling and ectopic activation of EGFR-Ras signaling in EBs is sufficient to drive EBs cell-autonomously to re-enter into mitosis. In addition, we examined whether EBs gain ISC identity as a prerequisite to divide, but the immunostaining with stem cell marker Delta shows that these dividing EBs do not gain ISC identity. After employing lineage tracing experiments, we further demonstrate that EBs dedifferentiate to generate functional ISCs after symmetric divisions of EBs. Together, our study in Drosophila intestines uncovers a new role of EGFR-Ras signaling in regulating re-entry into mitosis and dedifferentiation during regeneration and reveals a novel mechanism by which ISC progenies undergo dedifferentiation through a mitotic division, which has important implication to mammalian tissue homeostasis and tumorigenesis.

scholarly journals Long-term efficacy of mesenchymal stem cells implantation in combination with type I collagen membrane: a rat experimental model of rotator cuff tears

2012 ◽  
Vol 20 ◽  
pp. S277
Author(s):  
P. Tornero-Esteban ◽  
C. Rodriguez-Bobada ◽  
J. Hoyas ◽  
E. Villafuertes ◽  
F. Marco ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rotator Cuff ◽  
Experimental Model ◽  
Type I Collagen ◽  
Rotator Cuff Tears ◽  
Collagen Membrane ◽  
Type I ◽  
Term Efficacy
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