Defining the pericyte to fibroblast lineage
(English)Manuscript (preprint) (Other academic)
In the present study placental tissues were characterized in vivo with regards to markers expressed on pericytes, fibroblasts and collagen type I synthesis. Microvascular fragments (MVFs) isolated from human placentas had a phenotypical marker profile consistent with microvessels in situ. Cells emerging from MVFs from placenta express a marker profile consistent with a pericyte phenotype. Temporal studies identified three optimal time points (T0, T1 and T2) subsequent to the onset of cells emerging from MVFs for further analysis with regards to divergence in marker expression profiles. T0, T1 and T2 time points contained a population of cells with a cellular phenotype consistent with mesenchymal stem/progenitor cells, activated microvascular pericytes and mature connective tissue cells. Three discernable subpopulations of cells were identified i.e. Stro-1+/CD146+/podoplanin-, Stro-1-/CD146+/podoplanin- and Stro-1-/CD146-/podoplanin+ cells. Flow cytometry analysis allowed for the Stro-1-/CD146+/podoplanin- and Stro-1-/CD146-/podplanin+ cell populations to be further divided into 2 subgroups based on the expression of desmin, αSMA and TE-7. Five steps in the differentiation process from mesenchymal stem/progenitor cell to collagen type I producing fibroblast and the order by which they progressed could be defined by re-diversification studies i.e. ability of one population of cells to give rise to the other population of cells. Two in vivo experimental systems, TPA induced inflammation and excisional cutaneous wound healing were analyzed for the existence of slow cycling cells. The in vivo evidence shows that microvascular pericytes constitute a reservoir of stem/progenitor cells for pro-fibrotic connective tissue cells. This study presents novel evidence for a connective tissue cell lineage originating from a undifferentiated mesenchymal vessel associated cell population that via pericytes differentiate into pro-fibrotic fibroblasts.
pericyte fibroblast differentiation cell lineage mesenchymal stem cell
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Microbiology in the medical area Cell and Molecular Biology
Research subject Medical Biochemistry; Microbiology; Cell Research
IdentifiersURN: urn:nbn:se:uu:diva-132610OAI: oai:DiVA.org:uu-132610DiVA: diva2:359884