Up-Regulation of Superoxide Dismutase 2 in 3D Spheroid Formation Promotes Therapeutic Potency of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells
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 d...
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| Format: | Article |
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MDPI AG
2020-01-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/1/66 |
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| author | Miyoung Lee Bo Ram Song Dong Hyun Kim Jueun Ha Minju Lee Soo Jin Choi Wonil Oh Soyoun Um Hye Jin Jin |
| author_facet | Miyoung Lee Bo Ram Song Dong Hyun Kim Jueun Ha Minju Lee Soo Jin Choi Wonil Oh Soyoun Um Hye Jin Jin |
| author_sort | Miyoung Lee |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T18:14:17Z |
| format | Article |
| id | doaj.art-55983f4ad7a34841ac6abe4a09144160 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-12T18:14:17Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
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| series | Antioxidants |
| spelling | doaj.art-55983f4ad7a34841ac6abe4a091441602023-08-02T09:12:11ZengMDPI AGAntioxidants2076-39212020-01-01916610.3390/antiox9010066antiox9010066Up-Regulation of Superoxide Dismutase 2 in 3D Spheroid Formation Promotes Therapeutic Potency of Human Umbilical Cord Blood-Derived Mesenchymal Stem CellsMiyoung Lee0Bo Ram Song1Dong Hyun Kim2Jueun Ha3Minju Lee4Soo Jin Choi5Wonil Oh6Soyoun Um7Hye Jin Jin8Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, KoreaBiomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, KoreaBiomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, KoreaBiomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, KoreaBiomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, KoreaBiomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, KoreaBiomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, KoreaBiomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, KoreaBiomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, KoreaUmbilical 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.https://www.mdpi.com/2076-3921/9/1/66superoxide dismutase 2spheroidmesenchymal stem cellcell therapy |
| spellingShingle | Miyoung Lee Bo Ram Song Dong Hyun Kim Jueun Ha Minju Lee Soo Jin Choi Wonil Oh Soyoun Um Hye Jin Jin Up-Regulation of Superoxide Dismutase 2 in 3D Spheroid Formation Promotes Therapeutic Potency of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Antioxidants superoxide dismutase 2 spheroid mesenchymal stem cell cell therapy |
| title | Up-Regulation of Superoxide Dismutase 2 in 3D Spheroid Formation Promotes Therapeutic Potency of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells |
| title_full | Up-Regulation of Superoxide Dismutase 2 in 3D Spheroid Formation Promotes Therapeutic Potency of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells |
| title_fullStr | Up-Regulation of Superoxide Dismutase 2 in 3D Spheroid Formation Promotes Therapeutic Potency of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells |
| title_full_unstemmed | Up-Regulation of Superoxide Dismutase 2 in 3D Spheroid Formation Promotes Therapeutic Potency of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells |
| title_short | Up-Regulation of Superoxide Dismutase 2 in 3D Spheroid Formation Promotes Therapeutic Potency of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells |
| title_sort | up regulation of superoxide dismutase 2 in 3d spheroid formation promotes therapeutic potency of human umbilical cord blood derived mesenchymal stem cells |
| topic | superoxide dismutase 2 spheroid mesenchymal stem cell cell therapy |
| url | https://www.mdpi.com/2076-3921/9/1/66 |
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