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

Hristina Obradovic, Jelena Krstic, Drenka Trivanovic, Slavko Mojsilovic, Ivana Okic, Tamara Kukolj, Vesna Ilic, Aleksandra Jaukovic, Milan Terzic, Diana Bugarski

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

INTRODUCTION: 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.

METHODS: 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.

RESULTS: Compared to standard 21% O2, 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.

CONCLUSION: Culturing of WJ-MSCs under 3% O2 should be considered a credible condition when investigating their properties and potential use.

Original languageEnglish
Pages (from-to)25-34
Number of pages10
JournalPlacenta
Volume82
DOIs
Publication statusPublished - Jul 2019

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