Use this URL to cite or link to this record in EThOS:
Title: Assessing the functional heterogeneity of human perivascular cells
Author: Gomez Salazar, Mario Armando
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2020
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Thesis embargoed until 27 Jun 2021
Access from Institution:
Perivascular cells found in multiple organs give rise to mesenchymal stromal/stem cells or MSCs in vitro. These include adventitial cells (CD34+ CD146- CD31- CD45-) isolated from large vessels and pericytes (CD34- CD146+ CD31-CD45-) found in small vessels and capillaries. Both populations play a key role in tissue remodelling during injury and disease and display phenotypic and functional heterogeneity. However, specific stem cell properties of both populations are unknown. During my PhD, I have identified aldehyde dehydrogenase (ALDH) activity as a marker of stem cell-like perivascular cells. We performed RNA sequencing on perivascular cells isolated based upon high- or low ALDH activity. I found transcriptional differences that suggest different functions in vivo including progenitor capacity and interaction with the immune system. Interestingly, I found that ALDH1A1, which has been associated with stem cell properties, is the main isoform present in ALDH high adventitial cells suggesting their involvement in the regeneration process post-tissue injury. Whether these cells change in culture remains unclear. I found that ALDH subsets isolated from adventitial cells become similar both transcriptionally and functionally upon expansion in MSC culture. Conversely, pericytes seem to maintain a different identity compared to adventitial cells in vitro. I next analysed ALDH1A1 expression in pathological tissues. In human glioblastoma, I found that ALDH1A1 expression in perivascular cells changes suggesting their involvement in angiogenesis and tumour growth. Compared to control, skeletal muscle in mice post-injury showed changes in ALDH1A1 expression distribution, suggesting their contribution to the regeneration process. In conclusion, my results show that ALDH high adventitial cells in large vessels mark a population of MSC progenitors expressing genes involved in processes such as angiogenesis and, matrix remodelling, amongst others. Importantly, I documented how culture conditions change these perivascular cells once they become MSCs in vitro. Finally, I showed that ALDH1A1 expression and cell distribution in disease or after injury is altered.
Supervisor: Peault, Bruno ; Crisan, Mihaela Sponsor: Medical Research Council (MRC)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: mesenchymal stem cells ; pericytes ; perivascular stem cells ; cell detoxification ; ALDH1A1 ; ALDH activity