Hye Joung Kim1, Yong-Rim Kwon1, Yu-Jin Bae1, Yoo-Jin Kim2,3. 1. Laboratory of Hematological Disease and Transplant Immunology, Seoul, Republic of Korea. 2. Laboratory of Hematological Disease and Transplant Immunology, Seoul, Republic of Korea. yoojink@catholic.ac.kr. 3. Department of Hematology, Seoul St. Mary's Hospital, College of Medicine, Catholic Blood and Marrow Transplantation Center, Catholic University Of Korea, 505 Banpo-Dong, Seocho-Gu, Seoul, 137-701, Republic of Korea. yoojink@catholic.ac.kr.
Abstract
OBJECTIVE: To enhance the differentiation of mesenchymal stem cells (MSCs) and their epigenetic status by modification using hypomethylating agents (HMAs) and histone deacetylase inhibitors (HDACs). RESULTS: Treatment with 5-azacytidine or 5-azacytidine plus trichostatin A (TSA) increased expression of Runx-2, BDNF and Sox-9 compared with the control or TSA groups. Maximal increases of 4.1-, 4.5-, and 8.3-fold in Runx-2, BDNF, and Sox-9 transcript levels, respectively, were observed in the 5-azacytidine plus TSA group. Similar to the expression pattern of key regulatory molecules, differentiation to each lineage was also enhanced considerably in the 5-azacytidine or in the 5-azacytidine plus TSA groups. Quantitative analyses at the protein level showed 8.9-, 26.8-, 27.9-, and 28.5-fold upregulation of osterix, MAP-2, nestin, and type II collagen), respectively. CONCLUSION: HMAs and HDACs enhanced in vitro differentiation of MSCs, which was maximized when the two drugs were combined, with HMA having the dominant effect.
OBJECTIVE: To enhance the differentiation of mesenchymal stem cells (MSCs) and their epigenetic status by modification using hypomethylating agents (HMAs) and histone deacetylase inhibitors (HDACs). RESULTS: Treatment with 5-azacytidine or 5-azacytidine plus trichostatin A (TSA) increased expression of Runx-2, BDNF and Sox-9 compared with the control or TSA groups. Maximal increases of 4.1-, 4.5-, and 8.3-fold in Runx-2, BDNF, and Sox-9 transcript levels, respectively, were observed in the 5-azacytidine plus TSA group. Similar to the expression pattern of key regulatory molecules, differentiation to each lineage was also enhanced considerably in the 5-azacytidine or in the 5-azacytidine plus TSA groups. Quantitative analyses at the protein level showed 8.9-, 26.8-, 27.9-, and 28.5-fold upregulation of osterix, MAP-2, nestin, and type II collagen), respectively. CONCLUSION: HMAs and HDACs enhanced in vitro differentiation of MSCs, which was maximized when the two drugs were combined, with HMA having the dominant effect.
Authors: Judit Vágó; Katalin Kiss; Edina Karanyicz; Roland Takács; Csaba Matta; László Ducza; Tibor A Rauch; Róza Zákány Journal: Cells Date: 2021-10-06 Impact factor: 6.600