PMID- 32357508 OWN - NLM STAT- MEDLINE DCOM- 20210218 LR - 20210218 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 25 IP - 9 DP - 2020 Apr 26 TI - Preconditioning of Adipose-Derived Mesenchymal Stem-Like Cells with Eugenol Potentiates Their Migration and Proliferation In Vitro and Therapeutic Abilities in Rat Hepatic Fibrosis. LID - 10.3390/molecules25092020 [doi] LID - 2020 AB - Mesenchymal stem cells (MSCs) have considerable therapeutic abilities in various disorders, including hepatic fibrosis. They may be affected with different culture conditions. This study investigated, on molecular basics, the effect of pretreatment with eugenol on the characteristics of adipose tissue-derived MSCs (ASCs) in vitro and the implication of eugenol preconditioning on the in vivo therapeutic abilities of ASCs against CCl(4)-induced hepatic fibrosis in rats. The effect of eugenol on ASCs was assessed using viability, scratch migration and sphere formation assays. Expressions of genes and proteins were estimated by immunofluorescence or qRT-PCR. For the in vivo investigations, rats were divided into four groups: the normal control group, fibrotic (CCl(4)) group, CCl(4)+ASCs group and CCl(4) + eugenol-preconditioned ASCs (CCl(4)+E-ASCs) group. Eugenol affected the viability of ASCs in a concentration- and time-dependent manner. Eugenol improved their self-renewal, proliferation and migration abilities and significantly increased their expression of c-Met, reduced expression 1 (Rex1), octamer-binding transcription factor 4 (Oct4) and nanog genes. Furthermore, E-ASCs showed more of a homing ability than ASCs and improved the serum levels of ALT, AST, albumin, total bilirubin and hyaluronic acid more efficient than ASCs in treating CCl(4)-induced hepatic fibrosis, which was confirmed with histopathology. More interestingly, compared to the CCl(4)+ASCs group, CCl(4)+E-ASCs group showed a lower expression of inducible nitric oxide synthase (iNOS), monocyte chemoattractant protein-1 (MCP-1), cluster of differentiation 163 (CD163) and tumor necrosis factor-alpha (TNF-alpha) genes and higher expression of matrix metalloproteinase (MMP)-9 and MMP-13 genes. This study, for the first time, revealed that eugenol significantly improved the self-renewal, migration and proliferation characteristics of ASCs, in vitro. In addition, we demonstrated that eugenol-preconditioning significantly enhanced the therapeutic abilities of the injected ASCs against CCl(4)-induced hepatic fibrosis. FAU - Fathy, Moustafa AU - Fathy M AUID- ORCID: 0000-0002-0734-5007 AD - Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan. AD - Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt. FAU - Okabe, Motonori AU - Okabe M AD - Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan. FAU - M Othman, Eman AU - M Othman E AD - Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt. AD - Department of Bioinformatics, Biocenter, University of Wurzburg, Am Hubland, 97074 Wuerzburg, Germany. FAU - Saad Eldien, Heba M AU - Saad Eldien HM AD - Department of Anatomy, College of Medicine, Jouf University, Jouf, Saudi Arabia. FAU - Yoshida, Toshiko AU - Yoshida T AD - Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan. LA - eng PT - Journal Article DEP - 20200426 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, Myelomonocytic) RN - 0 (CD163 antigen) RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (Kruppel-Like Transcription Factors) RN - 0 (Nanog Homeobox Protein) RN - 0 (Nanog protein, rat) RN - 0 (Octamer Transcription Factor-3) RN - 0 (Pou5f1 protein, rat) RN - 0 (Receptors, Cell Surface) RN - 0 (Tumor Necrosis Factor-alpha) RN - 3T8H1794QW (Eugenol) RN - 9004-61-9 (Hyaluronic Acid) RN - CL2T97X0V0 (Carbon Tetrachloride) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - EC 3.4.24.- (Matrix Metalloproteinase 13) RN - EC 3.4.24.- (Mmp13 protein, rat) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - EC 3.4.24.35 (Mmp9 protein, rat) RN - RFM9X3LJ49 (Bilirubin) SB - IM MH - Animals MH - Antigens, CD/genetics/metabolism MH - Antigens, Differentiation, Myelomonocytic/genetics/metabolism MH - Bilirubin/blood MH - Carbon Tetrachloride/toxicity MH - Cell Movement/*drug effects MH - Cell Proliferation/*drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Chemokine CCL2/genetics/metabolism MH - Eugenol/*pharmacology MH - Gene Expression Regulation/drug effects MH - Hyaluronic Acid/blood MH - Kruppel-Like Transcription Factors/genetics/metabolism MH - Liver Cirrhosis/chemically induced/pathology/*therapy MH - Male MH - Matrix Metalloproteinase 13/genetics/metabolism MH - Matrix Metalloproteinase 9/genetics/metabolism MH - Mesenchymal Stem Cell Transplantation/*methods MH - Mesenchymal Stem Cells/cytology/*drug effects/enzymology/metabolism MH - Nanog Homeobox Protein/genetics/metabolism MH - Nitric Oxide Synthase Type II/genetics/metabolism MH - Octamer Transcription Factor-3/genetics/metabolism MH - Proto-Oncogene Proteins c-met/genetics/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Cell Surface/genetics/metabolism MH - Tumor Necrosis Factor-alpha/genetics/metabolism PMC - PMC7248858 OTO - NOTNLM OT - CCl4 OT - adipose tissue-derived MSCs OT - eugenol OT - hepatic fibrosis OT - migration OT - self-renewal COIS- The authors declare no conflict of interest. EDAT- 2020/05/03 06:00 MHDA- 2021/02/20 06:00 PMCR- 2020/04/26 CRDT- 2020/05/03 06:00 PHST- 2020/03/03 00:00 [received] PHST- 2020/04/18 00:00 [revised] PHST- 2020/04/24 00:00 [accepted] PHST- 2020/05/03 06:00 [entrez] PHST- 2020/05/03 06:00 [pubmed] PHST- 2021/02/20 06:00 [medline] PHST- 2020/04/26 00:00 [pmc-release] AID - molecules25092020 [pii] AID - molecules-25-02020 [pii] AID - 10.3390/molecules25092020 [doi] PST - epublish SO - Molecules. 2020 Apr 26;25(9):2020. doi: 10.3390/molecules25092020.