Cell-Based Therapy Of Human Adipose- Derived Mesenchymal Stem Cell Expressing Angiopoietin-1 In An Experimental Model Of Airway Inflammation
| dc.contributor.author | Nur Shuhaidatul Sarmiza Abdul Halim | |
| dc.date.accessioned | 2020-12-14T03:11:55Z | |
| dc.date.available | 2020-12-14T03:11:55Z | |
| dc.date.issued | 2018-09 | |
| dc.description.abstract | Cell-based therapy of mesenchymal stem cells (MSCs) has been shown to enhance the endogenous repair process by increasing the limited regenerative capacity of the lung in chronic lung disorders as well as following injury. However, the underlying cellular and molecular mechanisms of MSCs to enhance airway regeneration and repair are remain unclear. This study was aimed to investigate the effect of delivering human adipose-derived MSCs (hAD-MSCs) alone and in combination with vasculoprotective factor, the ANGPT1, by aerosol technique in a rabbit model of asthma related-airway inflammation. Given the anti-inflammatory, anti-permeability, and endothelial-protective characteristics of ANGPT1, we hypothesise that, combining MSCs with ANGPT1 offers promise in the treatment of airway inflammation. Transfection of hAD-MSCs with ANGPT1 was performed using microporation technique. For in vivo study, the rabbit were sensitised with combination of ovalbumin (Ova) and alum injection and further challenged with Ova inhalation to induce asthma-related airway inflammation. The MSCs and MSC-pANGPT1 were aerosolised directly into the airway using the MicroSprayer® Aerosolizer 48 h after injury. Histopathological assessments of the airway inflammation along with local inflammatory responses were quantitatively measured at three days after cell delivery. To investigate the functional effect of MSCs on airway regeneration and repair, an indirect in vitro co-culture model of injured airway epithelium explant with MSCs was developed. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was performed to determine the factors secreted by MSCs and their involvement in epithelium regeneration and repair was evaluated by histopathological assessment. The present study provides evidence that the microporation technique is superior to the others in terms of its ability to transfect hAD-MSCs without affecting the proliferation and differentiation capabilities of MSCs. Administration of aerosolised MSCs and MSC-pANGPT1 markedly reduced inflammation of the airways, as reflected by decreased of airway wall thickening and infiltration of granulocytes at the peribronchiale and perivascular regions. They also alleviated the number of airway inflammatory cells in the bronchoalveolar lavage (BAL) fluid and goblet cell hyperplasia. Administration of aerosolised MSC-pANGPT1 provided an additional effect merely in reducing the expression levels of various pro-inflammatory genes to the baseline values. In the co-culture assay, histological analysis provided strong evidence of the stimulatory behaviours of MSCs to enhance the migratory, proliferative and differentiation abilities of airway epithelial cells (AECs) in repairing the injured airway epithelium. Compounds secreted by MSCs also markedly initiated the epithelial-to-mesenchymal transition (EMT) process during early wound repair. The identification of 54 of MSC-secreted proteins of which approximately 43 of them were found to be involved in airway epithelial cell migration, proliferation, differentiation and initiation of EMT process. This occurrence further supports the evidence of MSCs stimulatory ability in accelerating airway regeneration and repair. This study provides cellular and molecular insights of MSC-based therapy to form a basis evidence for future treatment to treat lung injuries. | en_US |
| dc.identifier.uri | http://hdl.handle.net/123456789/10764 | |
| dc.language.iso | en | en_US |
| dc.publisher | Universiti Sains Malaysia | en_US |
| dc.subject | Cell-based therapy | en_US |
| dc.title | Cell-Based Therapy Of Human Adipose- Derived Mesenchymal Stem Cell Expressing Angiopoietin-1 In An Experimental Model Of Airway Inflammation | en_US |
| dc.type | Thesis | en_US |
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