Literature DB >> 24291741

Doxorubicin has in vivo toxicological effects on ex vivo cultured mesenchymal stem cells.

Maira Souza Oliveira1, Juliana Lott Carvalho2, Ana Carolina De Angelis Campos2, Dawidson Assis Gomes2, Alfredo Miranda de Goes2, Marília Martins Melo3.   

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.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Entities:  

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

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Year:  2013        PMID: 24291741     DOI: 10.1016/j.toxlet.2013.11.023

Source DB:  PubMed          Journal:  Toxicol Lett        ISSN: 0378-4274            Impact factor:   4.372


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