title: Factors enhancing the migration and the homing of mesenchymal stem cells in experimentally induced cardiotoxicity in rats.
abstract: Doxorubicin is an effective anti-neoplastic drug but its use is limited by its cardiotoxicity. Administration of mesenchymal stem cells (MSCs) for the management of cardiotoxicity was with poor myocardial homing capacity. With the aim of developing novel techniques to improve the migration of MSCs, we tested whether valproate and electric fields (EFs) direct the migration of MSCs towards the damaged myocardium. The study included five groups of female albino rats. The first group included 10 healthy rats as normal control group. The remaining 40 female rats received doxorubicin for induction of acute cardiotoxicity. Four rats were sacrificed for histopathological confirmation of cardiotoxicity. The remaining rats were equally divided into subsequent four groups. The second group included nine rats that did not receive further treatment (positive control group). The third group included nine rats which received intravenous bone marrow derived mesenchymal stem cells (BM-MSCs) after cardiotoxicity induction. The fourth group included nine rats which received BM-MSCs plus sodium valporate after cardiotoxicity induction. The fifth group included nine rats which received BM-MSCs plus sodium valporate after cardiotoxicity induction and were exposed to an electrical stimulation (ES). Blood samples were taken from all groups at the end of the study to estimate creatine kinase-MB (CK-MB), aspartate transaminase (AST) and lactate dehydrogenase (LDH). Heart tissues from all rats were used for RNA extraction for assessment of sry gene expression. Homing was tested by PKH26 fluorescence in myocardial tissue sections and by sry gene expression. The best biochemical and histopathological improvement in cardiotoxicity was demonstrated in group 5 (rats that received ES and valporate with MSCs). We concluded that EFs and sodium valproate enhance homing ability of MSCs towards the damaged myocardium in doxorubicin induced carditoxicity model. © 2017 IUBMB Life, 69(3):162-169, 2017.
authors.affiliation: Zoology Department, Physiology Section, Faculty of Science, Zagazig University, Egypt.
authors.forename: Nabil
authors.initials: N
authors.lastname: A Soliman
authors.affiliation: Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Zagazig University, Egypt.
authors.forename: Somia H
authors.initials: SH
authors.lastname: Abd-Allah
authors.affiliation: Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Zagazig University, Egypt.
authors.forename: Samia
authors.initials: S
authors.lastname: Hussein
authors.affiliation: Zoology Department, Physiology Section, Faculty of Science, Zagazig University, Egypt.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Alaa Eldeen
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D066126:Cardiotoxicity / Q000473:pathology / Q000628:therapy; D002465:Cell Movement; D002478:Cells, Cultured; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D004317:Doxorubicin / Q000009:adverse effects*; D005260:Female; D015870:Gene Expression; D024282:Genes, sry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D051381:Rats
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D052279:Creatine Kinase, MB Form
keywords: cardiotoxicity; electrical stimulation; homing; mesenchymal stem cells; valproate