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Merck

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

Toxicology letters (2013-12-03)
Maira Souza Oliveira, Juliana Lott Carvalho, Ana Carolina De Angelis Campos, Dawidson Assis Gomes, Alfredo Miranda de Goes, Marília Martins Melo
ZUSAMMENFASSUNG

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.

MATERIALIEN
Produktnummer
Marke
Produktbeschreibung

Sigma-Aldrich
Doxorubicin -hydrochlorid, 98.0-102.0% (HPLC)
Sigma-Aldrich
Doxorubicin -hydrochlorid, suitable for fluorescence, 98.0-102.0% (HPLC)
Sigma-Aldrich
Phosphatase, alkalisch aus Rinderdarmschleimhaut, buffered aqueous solution, ≥2,000 DEA units/mg protein
Sigma-Aldrich
Phosphatase, alkalisch aus Rinderdarmschleimhaut, lyophilized powder, ≥10 DEA units/mg solid
Sigma-Aldrich
Phosphatase, alkalisch aus Rinderdarmschleimhaut, BioUltra, ≥5,700 DEA units/mg protein
Doxorubicin -hydrochlorid, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Phosphatase, alkalisch aus E. coli, lyophilized powder, 30-60 units/mg protein (in glycine buffer)
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Phosphatase, alkalisch aus Rinderdarmschleimhaut, ≥5,500 DEA units/mg protein
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Phosphatase, alkalisch aus E. coli, buffered aqueous glycerol solution, 20-50 units/mg protein (in glycine buffer)
Sigma-Aldrich
Phosphatase, alkalisch aus Rinderdarmschleimhaut, buffered aqueous glycerol solution, ≥4,000 DEA units/mg protein
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Phosphatase, alkalisch aus E. coli, ammonium sulfate suspension, 30-90 units/mg protein (modified Warburg-Christian, in glycine buffer)
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Phosphatase, alkalisch aus Schweineniere, lyophilized powder, ≥100 DEA units/mg protein
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Phosphatase, alkalische Garnelen, ≥900 DEA units/mL, buffered aqueous glycerol solution, recombinant, expressed in proprietary host
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