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SHR Neuro Cancer Cardio Lipid Metab Microb

Obradovic, H; Krstic, J; Trivanovic, D; Mojsilovic, S; Okic, I; Kukolj, T; Ilic, V; Jaukovic, A; Terzic, M; Bugarski, D.
Improving stemness and functional features of mesenchymal stem cells from Wharton's jelly of a human umbilical cord by mimicking the native, low oxygen stem cell niche.
PLACENTA. 2019; 82(3): 25-34. Doi: 10.1016/j.placenta.2019.05.005
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Co-authors Med Uni Graz: Krstic Jelena
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Abstract:: Mesenchymal stem cells from Wharton's Jelly of a human umbilical cord (WJ-MSCs) are a potential tool in regenerative medicine based on their availability, proliferative potential and differentiation capacity. Since their physiological niche contains low oxygen levels, we investigated whether cultivation of WJ-MSCs at 3% O₂ affects their main features. WJ-MSCs were cultured under 21% and 3% O₂. Proliferation rate was followed by short and long term proliferation assays, clonogenic capacity by CFU-F assay and cell cycle and death by flow cytometry. Differentiation capacity was investigated by histochemical staining after induced differentiation. Pluripotency and differentiation markers' expression was determined by RT-PCR. Migration capacity was followed by scratch assay and mobilization from collagen, and the activity of proteolytic enzymes by zymography. Specific inhibitors of MAPK and Wnt/β-catenin pathways were used to investigate underlying molecular mechanisms. Compared to standard 21% O_2, cultivation of WJ-MSCs at 3% O₂ did not influence their immunophenotype, while it modulated their differentiation process and enhanced their clonogenic and expansion capacity. 3% O₂ induced transient change in cell cycle and prevented cell death. The expression of NANOG, OCT4A, OCT4B and SOX2 was increased at 3% O₂. Both cultivation and preculturing of WJ-MSCs at 3% O₂ increased their in vitro migratory capacity and enhanced the activity of proteolytic enzymes. ERK1/2 mediated WJ-MSCs' mobilization from collagen regardless of oxygen levels, while Wnt/β-catenin pathway was activated during migration and mobilization at standard conditions. Culturing of WJ-MSCs under 3% O₂ should be considered a credible condition when investigating their properties and potential use. Copyright © 2019 Elsevier Ltd. All rights reserved.
Find related publications in this database (Keywords): Mesenchymal stem cells (MSC); Wharton's jelly; Hypoxia; Stemness; Migration