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
