Next Article in Journal
The Apoplastic and Symplastic Antioxidant System in Onion: Response to Long-Term Salt Stress
Previous Article in Journal
Pholiota nameko Polysaccharides Promotes Cell Proliferation and Migration and Reduces ROS Content in H2O2-Induced L929 Cells
Previous Article in Special Issue
Assessment of Subcellular ROS and NO Metabolism in Higher Plants: Multifunctional Signaling Molecules
Open AccessArticle

Up-Regulation of Superoxide Dismutase 2 in 3D Spheroid Formation Promotes Therapeutic Potency of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells

Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Antioxidants 2020, 9(1), 66; https://doi.org/10.3390/antiox9010066
Received: 19 December 2019 / Revised: 6 January 2020 / Accepted: 9 January 2020 / Published: 11 January 2020
(This article belongs to the Special Issue Oxidative stress and Applied Biology)
Umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) are accessible, available in abundance, and have been shown to be a promising source that can regenerate cartilage in patients with osteoarthritis or other orthopedic diseases. Recently, a three-dimensional (3D) cell culture system was developed to mimic the naive tissue microenvironment. However, the efficacy of cells generated from the 3D spheroid culture system has not yet been elucidated. In the present study, we demonstrate the changes in superoxide dismutase 2 (SOD2) gene expression, an indicator of oxidative stress, on 3D spheroid MSCs. Moreover, siRNA transfection and neutralizing antibody investigations were performed to confirm the function of SOD2 and E-cadherin. Overall, we found that SOD2 siRNA transfection in the spheroid form of MSCs increases the expression of apoptotic genes and decreases the clearance of mitochondrial reactive oxygen species (ROS). As a result, we confirm that 3D spheroid formation increases E-cadherin and SOD2 expression, ultimately regulating the phosphoinositide 3-kinase (PI3K/pAkt/pNrf2 and pERK/pNrf2 signaling pathway. Additionally, we show that SOD2 expression on 3D spheroid MSCs affects the regeneration rates of destructive cartilage in an osteoarthritic model. We postulate that the impact of SOD2 expression on 3D spheroid MSCs reduces oxidative stress and apoptosis, and also promotes cartilage regeneration.
Keywords: superoxide dismutase 2; spheroid; mesenchymal stem cell; cell therapy superoxide dismutase 2; spheroid; mesenchymal stem cell; cell therapy
MDPI and ACS Style

Lee, M.; Song, B.R.; Kim, D.H.; Ha, J.; Lee, M.; Choi, S.J.; Oh, W.; Um, S.; Jin, H.J. Up-Regulation of Superoxide Dismutase 2 in 3D Spheroid Formation Promotes Therapeutic Potency of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells. Antioxidants 2020, 9, 66.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop