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Pericyte Dynamics in Glioblastoma and Ischemic Stroke

Buizza, Carolina LU (2025) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
Glioblastoma (GBM) and ischemic stroke represent two challenging brain pathologies which still lack an optimal therapeutic strategy. Central to these diseases are pericytes, mural cells that regulate blood-brain barrier (BBB) integrity, vascular stability, and immune responses. However, the diseasespecific alterations in pericytes that contribute to GBM progression and their influence on the poststroke cascade are still not fully understood. For these reasons, this thesis delves into the dynamic roles of pericytes in these pathologies, exploring their responses at the transcriptome, morphological, and secretome levels. We firstly addressed pericyte heterogeneity and defined their transcriptomic changes depending on the proximity to the... (More)
Glioblastoma (GBM) and ischemic stroke represent two challenging brain pathologies which still lack an optimal therapeutic strategy. Central to these diseases are pericytes, mural cells that regulate blood-brain barrier (BBB) integrity, vascular stability, and immune responses. However, the diseasespecific alterations in pericytes that contribute to GBM progression and their influence on the poststroke cascade are still not fully understood. For these reasons, this thesis delves into the dynamic roles of pericytes in these pathologies, exploring their responses at the transcriptome, morphological, and secretome levels. We firstly addressed pericyte heterogeneity and defined their transcriptomic changes depending on the proximity to the tumor in GBM (Paper I). This was followed by a temporal analysis of pericyte transcriptional responses during the acute phases of ischemic stroke (Paper II). Morphological studies in Papers III and IV provided insights into pericyte detachment, activation, and their role in BBB disruption and vascular remodeling following ischemic stroke. Lastly, Paper V investigated the changes in the pericyte secretome under hypoxic conditions in vitro. We found that in GBM, pericytes in the tumor vicinity showed increased gene expression and enhanced communication with immune cells. In ischemic stroke, we observed that pericytes responded rapidly within the first hour, and over time formed a distinct stroke-specific cluster, characterized by unique transcriptional changes. Additionally, under hypoxic conditions, pericytes altered their secretome, highlighting their dynamic response to the ischemic environment. By integrating findings across GBM and ischemic stroke, this thesis underscores the dynamic and plastic nature of pericytes, highlighting their critical role in extracellular matrix remodeling, vascular regulation, and immune modulation. The results position pericytes as promising therapeutic targets for improving outcomes in brain diseases. Future studies will benefit from further exploration of pericyte interactions within the broader cellular landscape of the brain. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • PhD Keller, Annika, Department of Neurosurgery, Zurich University Hospital & Zurich University
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Pericyte, Glioblastoma (GBM), Ischemic stroke, Transcriptome, Secretome, Diabetes, Blood-brain barrier
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2025:26
pages
99 pages
publisher
Lund University, Faculty of Medicine
defense location
Segerfalksalen, BMC A10, Sölvegatan 17 i Lund
defense date
2025-03-14 08:00:00
ISSN
1652-8220
ISBN
978-91-8021-679-1
language
English
LU publication?
yes
id
1be2e88d-4a20-49e0-92d0-bdff19f670f0
date added to LUP
2025-02-06 10:55:04
date last changed
2025-04-04 15:05:43
@phdthesis{1be2e88d-4a20-49e0-92d0-bdff19f670f0,
  abstract     = {{Glioblastoma (GBM) and ischemic stroke represent two challenging brain pathologies which still lack an optimal therapeutic strategy. Central to these diseases are pericytes, mural cells that regulate blood-brain barrier (BBB) integrity, vascular stability, and immune responses. However, the diseasespecific alterations in pericytes that contribute to GBM progression and their influence on the poststroke cascade are still not fully understood. For these reasons, this thesis delves into the dynamic roles of pericytes in these pathologies, exploring their responses at the transcriptome, morphological, and secretome levels. We firstly addressed pericyte heterogeneity and defined their transcriptomic changes depending on the proximity to the tumor in GBM (Paper I). This was followed by a temporal analysis of pericyte transcriptional responses during the acute phases of ischemic stroke (Paper II). Morphological studies in Papers III and IV provided insights into pericyte detachment, activation, and their role in BBB disruption and vascular remodeling following ischemic stroke. Lastly, Paper V investigated the changes in the pericyte secretome under hypoxic conditions in vitro. We found that in GBM, pericytes in the tumor vicinity showed increased gene expression and enhanced communication with immune cells. In ischemic stroke, we observed that pericytes responded rapidly within the first hour, and over time formed a distinct stroke-specific cluster, characterized by unique transcriptional changes. Additionally, under hypoxic conditions, pericytes altered their secretome, highlighting their dynamic response to the ischemic environment. By integrating findings across GBM and ischemic stroke, this thesis underscores the dynamic and plastic nature of pericytes, highlighting their critical role in extracellular matrix remodeling, vascular regulation, and immune modulation. The results position pericytes as promising therapeutic targets for improving outcomes in brain diseases. Future studies will benefit from further exploration of pericyte interactions within the broader cellular landscape of the brain.}},
  author       = {{Buizza, Carolina}},
  isbn         = {{978-91-8021-679-1}},
  issn         = {{1652-8220}},
  keywords     = {{Pericyte; Glioblastoma (GBM); Ischemic stroke; Transcriptome; Secretome; Diabetes; Blood-brain barrier}},
  language     = {{eng}},
  number       = {{2025:26}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Pericyte Dynamics in Glioblastoma and Ischemic Stroke}},
  url          = {{https://lup.lub.lu.se/search/files/207858051/Carolina_Buizza.pdf}},
  year         = {{2025}},
}