title: Doxorubicin has in vivo toxicological effects on ex vivo cultured mesenchymal stem cells.
abstract: Doxorubicin (dox) is an effective chemotherapeutic agent that leads to cardiotoxicity. An alternative treatment for dox-cardiotoxicity is autologous mesenchymal stem cells (MSCs) transplantation. It remains unclear if dox has deleterious effects on MSCs from subjects under chemotherapy, therefore this study aimed to evaluate dox in vivo toxicological effects on ex vivo cultured MSCs, inferring whether autologous transplantation may be an alternative treatment in patients who are exposed to the drug. Wistar rats received either dox or saline. Following treatments, animals were sacrificed and bone marrow MSCs were isolated, characterized for cell surface markers and assessed according to their viability, alkaline phosphatase production, and proliferation kinetics. Moreover, MSCs were primed to cardiac differentiation and troponin T and connexin 43 expressions were evaluated. Compared to control, undifferentiated MSCs from dox group kept the pattern for surface marker and had similar viability results. In contrast, they showed lower alkaline phosphatase production, proliferation rate, and connexin 43 expression. Primed MSCs from dox group showed lower troponin T levels. It was demonstrated a toxic effect of dox in host MSCs. This result renders the possibility of autologous MSCs transplantation to treat dox-cardiotoxicity, which could be a non-suitable option for subjects receiving such antineoplastic agent.
authors.affiliation: College of Veterinary Medicine, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Caixa Postal 567, 30123-970 Belo Horizonte, MG, Brazil. Electronic address: maira_oliveira@yahoo.com.
authors.forename: Maira Souza
authors.initials: MS
authors.lastname: Oliveira
authors.affiliation: Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Caixa Postal 567, 30123-970 Belo Horizonte, MG, Brazil.
authors.forename: Juliana Lott
authors.initials: JL
authors.lastname: Carvalho
authors.affiliation: Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Caixa Postal 567, 30123-970 Belo Horizonte, MG, Brazil.
authors.forename: Ana Carolina De Angelis
authors.initials: AC
authors.lastname: Campos
authors.affiliation: Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Caixa Postal 567, 30123-970 Belo Horizonte, MG, Brazil.
authors.forename: Dawidson Assis
authors.initials: DA
authors.lastname: Gomes
authors.affiliation: Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Caixa Postal 567, 30123-970 Belo Horizonte, MG, Brazil.
authors.forename: Alfredo Miranda
authors.initials: AM
authors.lastname: de Goes
authors.affiliation: College of Veterinary Medicine, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Caixa Postal 567, 30123-970 Belo Horizonte, MG, Brazil.
authors.forename: Marília Martins
authors.initials: MM
authors.lastname: Melo
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018031:Connexin 43 / Q000096:biosynthesis; D004317:Doxorubicin / Q000633:toxicity*; D019084:Fluorescent Antibody Technique, Indirect; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology; D032383:Myocytes, Cardiac / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000187:drug effects*; D020107:Troponin T / Q000096:biosynthesis
chemical_list: D000903:Antibiotics, Antineoplastic; D018031:Connexin 43; D008565:Membrane Proteins; D020107:Troponin T; D004317:Doxorubicin; D000469:Alkaline Phosphatase
keywords: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; 5-bromo-4-chloro-3-indolyl phosphate; AP; BCIP; BSA; Cardiac differentiation; Cell therapy; DMEM; Drug toxicity; Dulbecco's modified Eagle's medium; FBS; MSCs; MTT; Mesenchymal stem cells; NBT; PBS; PVDF; SDS; TBS; TBST; alkaline phosphatase; bovine serum albumin; dox; doxorubicin; fetal bovine serum; mesenchymal stem cells; nitroblue tetrazolium salt; phosphate buffered saline; polyvinylidene difluoride; sodium dodecyl sulfate; tris buffered saline; tris buffered saline with Tween