PMID- 32977637 OWN - NLM STAT- MEDLINE DCOM- 20210223 LR - 20210223 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 21 IP - 19 DP - 2020 Sep 23 TI - Ethionamide Preconditioning Enhances the Proliferation and Migration of Human Wharton's Jelly-Derived Mesenchymal Stem Cells. LID - 10.3390/ijms21197013 [doi] LID - 7013 AB - Mesenchymal stem cells (MSCs) are a useful source for cell-based therapy of a variety of immune-mediated diseases, including neurodegenerative disorders. However, poor migration ability and survival rate of MSCs after brain transplantation hinder the therapeutic effects in the disease microenvironment. Therefore, we attempted to use a preconditioning strategy with pharmacological agents to improve the cell proliferation and migration of MSCs. In this study, we identified ethionamide via the screening of a drug library, which enhanced the proliferation of MSCs. Preconditioning with ethionamide promoted the proliferation of Wharton's jelly-derived MSCs (WJ-MSCs) by activating phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase/extracellular signal-regulated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)1/2 signaling. Preconditioning with ethionamide also enhanced the migration ability of MSCs by upregulating expression of genes associated with migration, such as C-X-C motif chemokine receptor 4 (CXCR4) and C-X-C motif chemokine ligand 12 (CXCL12). Furthermore, preconditioning with ethionamide stimulated the secretion of paracrine factors, including neurotrophic and growth factors in MSCs. Compared to naive MSCs, ethionamide-preconditioned MSCs (ETH-MSCs) were found to survive longer in the brain after transplantation. These results suggested that enhancing the biological process of MSCs induced by ethionamide preconditioning presents itself as a promising strategy for enhancing the effectiveness of MSCs-based therapies. FAU - Lee, Na-Hee AU - Lee NH AD - Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. AD - Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. AD - Neuroscience Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. AD - Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. FAU - Myeong, Su Hyeon AU - Myeong SH AD - Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. AD - Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. AD - Neuroscience Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. AD - Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. FAU - Son, Hyo Jin AU - Son HJ AD - Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. AD - Neuroscience Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. AD - Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. AD - School of Medicine, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. FAU - Hwang, Jung Won AU - Hwang JW AD - Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. AD - Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. AD - Neuroscience Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. AD - Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. FAU - Lee, Na Kyung AU - Lee NK AUID- ORCID: 0000-0001-6116-2562 AD - Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. AD - School of Medicine, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. AD - Samsung Alzheimer Research Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. FAU - Chang, Jong Wook AU - Chang JW AD - Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. AD - R & D Center, ENCell Co. Ltd., Seoul 06072, Korea. FAU - Na, Duk L AU - Na DL AD - Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. AD - Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. AD - Neuroscience Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. AD - Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. AD - Samsung Alzheimer Research Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. LA - eng GR - HI14C3484/Ministry of Health and Welfare/ GR - HI18C0560/Ministry of Health and Welfare/ GR - NRF-2016R1D1A1B03933228/National research foundation/ PT - Journal Article DEP - 20200923 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - OAY8ORS3CQ (Ethionamide) SB - IM MH - Animals MH - Brain/cytology/metabolism MH - Cell Movement/*drug effects MH - Cell Proliferation/*drug effects MH - Ethionamide/*pharmacology MH - Gene Expression Regulation/*drug effects MH - Heterografts MH - Humans MH - MAP Kinase Signaling System/*drug effects MH - Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/cytology/*metabolism MH - Mice PMC - PMC7583833 OTO - NOTNLM OT - ethionamide-preconditioned MSCs (ETH-MSCs) OT - mesenchymal stem cells (MSCs) OT - migration OT - paracrine factors OT - proliferation OT - survival COIS- The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. EDAT- 2020/09/27 06:00 MHDA- 2021/02/24 06:00 PMCR- 2020/10/01 CRDT- 2020/09/26 01:01 PHST- 2020/08/21 00:00 [received] PHST- 2020/09/20 00:00 [revised] PHST- 2020/09/21 00:00 [accepted] PHST- 2020/09/26 01:01 [entrez] PHST- 2020/09/27 06:00 [pubmed] PHST- 2021/02/24 06:00 [medline] PHST- 2020/10/01 00:00 [pmc-release] AID - ijms21197013 [pii] AID - ijms-21-07013 [pii] AID - 10.3390/ijms21197013 [doi] PST - epublish SO - Int J Mol Sci. 2020 Sep 23;21(19):7013. doi: 10.3390/ijms21197013.