Development of hybrid microcarriers for stem cell therapy in COPD models ex vivo
(2021) MOBN03 20202Degree Projects in Molecular Biology
- Abstract
- Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by an accelerated decline in lung function due to narrowing and fibrosis of small airways and irreversible alveolar tissue destruction termed as emphysema. To date, no effective treatments exist which can reverse the damaged state of the affected lungs. Stem cell therapy represents a promising approach for targeting COPD. This project aimed to develop a novel stem cell therapy by use of custom-made microcarriers in ex vivo models of COPD. Hybrid microcarriers composed of decellularized extracellular matrix (dECM) and alginate were fabricated using microfluidics and tested for A549 cell growth in dynamic cell culturing conditions using spinner flasks.... (More)
- Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by an accelerated decline in lung function due to narrowing and fibrosis of small airways and irreversible alveolar tissue destruction termed as emphysema. To date, no effective treatments exist which can reverse the damaged state of the affected lungs. Stem cell therapy represents a promising approach for targeting COPD. This project aimed to develop a novel stem cell therapy by use of custom-made microcarriers in ex vivo models of COPD. Hybrid microcarriers composed of decellularized extracellular matrix (dECM) and alginate were fabricated using microfluidics and tested for A549 cell growth in dynamic cell culturing conditions using spinner flasks. Synthesis parameters were optimised in order to achieve stable hybrid microcarriers supportive for cell growth. For ex vivo COPD-modelling, mouse and human precision cut lung slices (PCLS) were exposed to elastase, trypsin, H2O2, or a combination of all three (COPD cocktail) for either 24h or 24h and a subsequent 24h recovery period (48h treatment). We found that particularly elastase and our cocktail induced COPD-like changes on the cellular as well as on the matrix level, as reflected by changes in alveolar epithelial cell markers Sftpc, Aqp5 and Hopx and distorted tissue morphology. In the future, our model can be employed for ex vivo testing of novel stem cell therapies, such as delivery of cell-bearing hybrid microcarriers, in the 3D natural lung environment. Moreover, our model is applicable to human PCLS cultures ex vivo and thus, holds great potential for studying and screening novel therapeutic strategies. (Less)
- Popular Abstract
- The lung disease, chronic obstructive pulmonary disease (COPD) is the third-leading cause of death worldwide and imposes a major economic burden on national health resources. In COPD airflow is reduced and patients experience difficulties breathing. The reduction of airflow is due to the destruction of gas exchanging tissue in the distal lung, resulting in the occurrence of large airspaces, termed emphysema. To date, no effective treatments exist capable of reversing the damaged state of affected lungs. Stem cell therapy provides an exciting opportunity for diseases, such as COPD in which tissue structure is damaged and lost. Stem cells are the body’s “raw material” from which all other cells with specialized function are generated. In... (More)
- The lung disease, chronic obstructive pulmonary disease (COPD) is the third-leading cause of death worldwide and imposes a major economic burden on national health resources. In COPD airflow is reduced and patients experience difficulties breathing. The reduction of airflow is due to the destruction of gas exchanging tissue in the distal lung, resulting in the occurrence of large airspaces, termed emphysema. To date, no effective treatments exist capable of reversing the damaged state of affected lungs. Stem cell therapy provides an exciting opportunity for diseases, such as COPD in which tissue structure is damaged and lost. Stem cells are the body’s “raw material” from which all other cells with specialized function are generated. In stem cell therapy these cells are transplanted into damaged or injured body regions in order to give rise to new but specialized cells. This project aimed to fabricate a vehicle capable of delivering lung stem cells into diseased COPD lungs for the purpose of regeneration. In this study, we successfully generated such a vehicle, by using a combination of a biological material obtained from the ocean along with a powder composed of building blocks on which cells sit. For optimization of the vehicle characteristics this project tested varying fabrication parameters and different biological materials. Moreover, in order to test our stem cell therapy, we established a model in fine lung slices – either of mouse or human nature – that was capable of mimicking features of the COPD disease. For this model we treated the lung slices with substances that are known to harm and cleave tissue components. We found that particularly an agent called, elastase, induced COPD-like characteristics in our model. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9066649
- author
- Thurner, Larissa Alina
- supervisor
- organization
- course
- MOBN03 20202
- year
- 2021
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9066649
- date added to LUP
- 2021-10-08 12:00:52
- date last changed
- 2021-10-08 12:00:52
@misc{9066649,
abstract = {{Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by an accelerated decline in lung function due to narrowing and fibrosis of small airways and irreversible alveolar tissue destruction termed as emphysema. To date, no effective treatments exist which can reverse the damaged state of the affected lungs. Stem cell therapy represents a promising approach for targeting COPD. This project aimed to develop a novel stem cell therapy by use of custom-made microcarriers in ex vivo models of COPD. Hybrid microcarriers composed of decellularized extracellular matrix (dECM) and alginate were fabricated using microfluidics and tested for A549 cell growth in dynamic cell culturing conditions using spinner flasks. Synthesis parameters were optimised in order to achieve stable hybrid microcarriers supportive for cell growth. For ex vivo COPD-modelling, mouse and human precision cut lung slices (PCLS) were exposed to elastase, trypsin, H2O2, or a combination of all three (COPD cocktail) for either 24h or 24h and a subsequent 24h recovery period (48h treatment). We found that particularly elastase and our cocktail induced COPD-like changes on the cellular as well as on the matrix level, as reflected by changes in alveolar epithelial cell markers Sftpc, Aqp5 and Hopx and distorted tissue morphology. In the future, our model can be employed for ex vivo testing of novel stem cell therapies, such as delivery of cell-bearing hybrid microcarriers, in the 3D natural lung environment. Moreover, our model is applicable to human PCLS cultures ex vivo and thus, holds great potential for studying and screening novel therapeutic strategies.}},
author = {{Thurner, Larissa Alina}},
language = {{eng}},
note = {{Student Paper}},
title = {{Development of hybrid microcarriers for stem cell therapy in COPD models ex vivo}},
year = {{2021}},
}