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@PHDTHESIS{GonzalezRubio:1013938,
author = {Gonzalez Rubio, Julian},
othercontributors = {Thiebes, Anja Lena and Cornelissen, Christian Gabriel},
title = {{T}issue-engineered vascularized models: from airway-virus
interaction to mesenchymal stromal cell potential},
school = {Rheinisch-Westfälische Technische Hochschule Aachen},
type = {Dissertation},
address = {Aachen},
publisher = {RWTH Aachen University},
reportid = {RWTH-2025-05808},
pages = {1 Online-Ressource : Illustrationen},
year = {2025},
note = {Veröffentlicht auf dem Publikationsserver der RWTH Aachen
University; Dissertation, Rheinisch-Westfälische Technische
Hochschule Aachen, 2025, Kumulative Dissertation},
abstract = {Traditional in vitro models such as 2D cell cultures fail
to recapitulate the complex microenvironment of in vivo
tissues and their pathological processes. In contrast, 3D
tissue-engineered models provide a more biomimetic platform,
integrating multiple cell types and native-like
organization. Thus, this thesis aims to apply a novel
vascularized model to investigate the airway tissue response
to viral particles and to improve the reproducibility of
future models by inclusion of induced pluripotent stem cell
(iPSC)-derived supporting cells. The first study explores
how SARS-CoV-2 particles affect airway epithelial
differentiation and barrier integrity. Treating vascularized
3D airway models comprising endothelial cells, tracheal
mesenchymal cells, and airway epithelial cells with
ultraviolet-irradiated virus particles strongly induces cell
ciliation. This occurs through the increase of FOXJ1 and
pPAK1/2, leading to the differentiation of basal and club
cells. The viral particles also disrupt tight junctions and
impair barrier function, shedding light on early epithelial
responses critical for understanding respiratory infectious
diseases like COVID-19.The second study uses a microfluidic
organ-on-a-chip to investigate iPSC-derived mesenchymal
stromal cells (iMSCs) as a potential alternative for primary
MSCs in vascularized models. Primary MSCs, unlike iMSCs,
markedly enhance vascularization by stimulating endothelial
cells to form interconnected vessels, supported by
pro-angiogenic signaling pathways and close perivascular
association. Although this demonstrates that iMSCs are not
suitable as substitutes for primary mesenchymal cells in
vascularized models, they emerge as a scalable and safer
alternative for regenerative therapies in conditions
involving pathological vascularization. Together, these
studies demonstrate the versatility of tissue-engineered
vascularized models for elucidating disease mechanisms and
advancing cell-based therapies in respiratory and vascular
contexts.},
cin = {811001-1 ; 923510},
ddc = {610},
cid = {$I:(DE-82)811001-1_20140620$},
pnm = {DFG project G:(GEPRIS)496706372 - Lost in Granulation -
Respiratorisches Mukosa-Modell zur In-vitro-Analyse von
Gewebegranulation durch mechanische Stimuli (496706372) /
DFG project G:(GEPRIS)495328185 -
Niederdruck-Rasterelektronenmikroskop (495328185) / GRK 2415
- GRK 2415: Mechanobiology in Epithelial 3D Tissue
Constructs (363055819) / BMBF 031B1150B - Modellregion,
Bio4MatPro: BoostLab 4-1 - PleuraPlug,
Oberflächenfunktionalisierte biobasierte und injizierbare
Pflaster zur Geweberegeneration bei traumatischen
Pleuraverletzungen, TP B (031B1150B) / BMBF 03VP11580 -
Biomarker zur Qualitätskontrolle von pluripotenten
Stammzellen - PluripotencyScreen (03VP11580) / VW Az 99078 -
Disease X-Chip (Az 99078)},
pid = {G:(GEPRIS)496706372 / G:(GEPRIS)495328185 /
G:(GEPRIS)363055819 / G:(BMBF)031B1150B / G:(BMBF)03VP11580
/ G:(VW)Az 99078},
typ = {PUB:(DE-HGF)11},
doi = {10.18154/RWTH-2025-05808},
url = {https://publications.rwth-aachen.de/record/1013938},
}
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