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.

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

Obradovic H ，Krstic J ，Trivanovic D ，Mojsilovic S ，Okic I ，Kukolj T ，Ilic V ，Jaukovic A ，Terzic M ，Bugarski D ... -  《-》

Differential expression of cell cycle and WNT pathway-related genes accounts for differences in the growth and differentiation potential of Wharton's jelly and bone marrow-derived mesenchymal stem cells.

Batsali AK ，Pontikoglou C ，Koutroulakis D ，Pavlaki KI ，Damianaki A ，Mavroudi I ，Alpantaki K ，Kouvidi E ，Kontakis G ，Papadaki HA ... -  《Stem Cell Research & Therapy》

Hypoxia with Wharton's jelly mesenchymal stem cell coculture maintains stemness of umbilical cord blood-derived CD34(+) cells.

Zhao D ，Liu L ，Chen Q ，Wang F ，Li Q ，Zeng Q ，Huang J ，Luo M ，Li W ，Zheng Y ，Liu T ... -  《Stem Cell Research & Therapy》

Biomimetic microenvironmental preconditioning enhance neuroprotective properties of human mesenchymal stem cells derived from Wharton's Jelly (WJ-MSCs).

Lech W ，Sarnowska A ，Kuczynska Z ，Dabrowski F ，Figiel-Dabrowska A ，Domanska-Janik K ，Buzanska L ，Zychowicz M ... -  《Scientific Reports》

Increased proliferation and analysis of differential gene expression in human Wharton's jelly-derived mesenchymal stromal cells under hypoxia.

Nekanti U ，Dastidar S ，Venugopal P ，Totey S ，Ta M ... -  《International Journal of Biological Sciences》