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Difluoromethylornithine stimulates early cardiac commitment of mesenchymal stem cells in a model of mixed culture with cardiomyocytes
Author(s) -
Muscari Claudio,
Bonafé Francesca,
Carboni Marco,
Govoni Marco,
Stanic Ivana,
Gamberini Chiara,
Ricci Francesca,
Tazzari Pier Luigi,
Caldarera Claudio Marcello,
Guarnieri Carlo
Publication year - 2008
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21683
Subject(s) - mesenchymal stem cell , polyamine , microbiology and biotechnology , cellular differentiation , biology , bone marrow , chemistry , immunology , biochemistry , gene
Abstract The efficiency of in vitro mesenchymal stem cell (MSC) differentiation into the myocardial lineage is generally poor. In order to improve cardiac commitment, bone marrow GFP + MSCs obtained from transgenic rats were cultured with adult wild type rat cardiomyocytes for 5 days in the presence of difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis and cell proliferation. The percentage of GFP + MSCs showing cardiac myofibril proteins (cMLC2, cTnI) was about threefold higher after DFMO addition (3%) relative to the untreated control (1%). Another set of experiments was performed with cardiomyocytes incubated for 1 day in the absence of glucose and serum and under hypoxic conditions (pO 2  < 1%), in order to simulate severe ischemia. The percentage of cardiac committed GFP + MSCs was about 5% when cultured with the hypoxic/starved cardiomyocytes and further increased to 7% after DFMO addition. The contemporary presence of putrescine in DFMO‐treated cells markedly blunted differentiation, while the cytostatic mitomycin C was not able to induce cardiac commitment. The involvement of histone acetylation in DFMO‐induced differentiation was evidenced by the strong attenuation of cardiac commitment exerted by anacardic acid, an inhibitor of histone acetylase. Moreover, the percentage of acetylated histone H3 significantly increased in bone marrow MSCs obtained from wild type rats and treated with DFMO. These results suggest that polyamine depletion can represent a useful strategy to improve MSC differentiation into the cardiac lineage, especially in the presence of cardiomyocytes damaged by an ischemic environment. J. Cell. Biochem. 103: 1046–1052, 2008. © 2008 Wiley‐Liss, Inc.

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