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

Autor:	Lee M; Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea., Song BR; Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea., Kim DH; Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea., Ha J; Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea., Lee M; Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea., Choi SJ; Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea., Oh W; Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea., Um S; Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea., Jin HJ; Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea.
Jazyk:	angličtina
Zdroj:	Antioxidants (Basel, Switzerland) [Antioxidants (Basel)] 2020 Jan 11; Vol. 9 (1). Date of Electronic Publication: 2020 Jan 11.
DOI:	10.3390/antiox9010066
Abstrakt:	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. Competing Interests: ERK: Extracellular signal-regulated kinases
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu