Chronic asthma and Mesenchymal stem cells: Hyaluronan and airway remodeling
| Autor: | Tracey L. Bonfield, Mark E. Lauer, Arnold I. Caplan, Benjamin D. Goldstein |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Clinical Biochemistry Inflammation Masson's trichrome stain Extracellular matrix 03 medical and health sciences 0302 clinical medicine In vivo medicine Fibroblast Hyaluronan biology business.industry Research Mesenchymal stem cell lcsh:RM1-950 Cell Biology In vitro Cell biology Ovalbumin 030104 developmental biology medicine.anatomical_structure lcsh:Therapeutics. Pharmacology 030228 respiratory system biology.protein Mesenchymal stem cells Collagen medicine.symptom business |
| Zdroj: | Journal of Inflammation (London, England) Journal of Inflammation, Vol 14, Iss 1, Pp 1-9 (2017) |
| ISSN: | 1476-9255 |
| Popis: | Background Previous studies have demonstrated that ovalbumin sensitization promotes chronic asthma phenotype in murine asthma model. Human mesenchymal stem cells (hMSCs) are multipotent cells in vitro that have been shown to decrease inflammation and can reverse airway remodeling when infused into an in vivo chronic asthma model. However, the mechanism by which hMSCs reverse remodeling is still unclear. In this study, we hypothesized that hMSCs influence remodeling by decreasing extracellular matrix (ECM) deposition, more specifically by decreasing collagen I, collagen III, and hyaluronan synthesis. Methods Chronic asthma phenotype was produced in an in vitro model with 3 T3 murine airway fibroblast cells by stimulating with GM-CSF. Collagen I and collagen III gene expression was investigated using RT-PCR and Taqman techniques. Hyaluronan was evaluated using FACE and Western Blots. The chronic asthma phenotype was produced in vivo in murine model using sensitization with ovalbumin with and without hMSC infusion therapy. ECM deposition (specifically trichrome staining, soluble and insoluble collagen deposition, and hyaluronan production) was evaluated. Image quantification was used to monitor trichrome staining changes. Results GM-CSF which induced collagen I and collagen III production was down-regulated with hMSC using co-culture. In the in vivo model, Ovalbumin induced enhanced ECM deposition, soluble and insoluble collagen production, and lung elastance. hMSC infusions decreased ECM deposition as evidenced by decreases in soluble and insoluble collagen production. Conclusion hMSCs participate in improved outcomes of remodeling by reversing excess collagen deposition and changing hyaluronan levels. |
| Databáze: | OpenAIRE |
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