Résumé
BACKGROUND AND OBJECTIVES: Most studies in cardiac regeneration have explored bone marrow mesenchymal stem cells (BM-MSC) with variable therapeutic effects. Amniotic fluid MSC (AF-MSC) having extended self-renewal and multi-potent properties may be superior to bone marrow MSC (BM-MSC). However, a comparison of their cardiomyogenic potency has not been studied yet.METHODS: The 5-azacytidine (5-aza) treated AF-MSC and BM-MSC were evaluated for the expression of GATA-4, Nkx2.5 and ISL-1 transcripts and proteins by quantitative RT-PCR and Western blotting, respectively as well as for the expression of cardiomyogenic differentiation markers cardiac troponin-T (cTNT), beta myosin heavy chain (βMHC) and alpha sarcomeric actinin (ASA) by immunocytochemistry.RESULTS: The AF-MSC as compared to BM-MSC had significantly higher expression of GATA-4 (183.06±29.85 vs. 9.80±0.05; p<0.01), Nkx2.5 (8.3±1.4 vs. 1.82±0.32; p<0.05), and ISL-1 (39.59±4.05 vs. 4.36±0.39; p<0.01) genes as well as GATA-4 (2.01±0.5 vs. 0.6±0.1; p<0.05), NKx2.5 (1.9±0.14 vs. 0.8±0.2; p<0.01) and ISL-1 (1.7±0.3 vs. 0.9±0.1; p<0.05) proteins. The AF-MSC also had significantly elevated expression of cTNT (5.0×10⁴±0.6×10⁴ vs. 3.5 ×10⁴±0.8×10⁴; p<0.01), β-MHC (15.7×10⁴±0.9×10⁴ vs. 8.2×10⁴±0.6×10⁴; p<0.01) and ASA (18.6×10⁴±4.9×10⁴ vs. 13.1×10⁴±3.0×10⁴; p<0.05) than BM-MSC.CONCLUSIONS: Our data suggest that AF-MSC have greater cardiomyogenic potency than BM-MSC, and thus may be a better source of MSC for therapeutic applications in cardiac regenerative medicine.
Sujets)
Femelle , Humains , Actinine , Liquide amniotique , Antigènes de différenciation , Azacitidine , Technique de Western , Moelle osseuse , Immunohistochimie , Cellules souches mésenchymateuses , Régénération , Médecine régénérative , Utilisations thérapeutiques , Troponine T , Myosines ventriculairesRésumé
Prognosis of acute myeloid leukemia relies heavily on the cytogenetic and molecular abnormalities. AML1-ETO fusion protein resulting from t[8;21], a recurring cytogenetic abnormality, is known to be associated with favorable prognosis. Additional molecular defects may, however, co-operate with the fusion proteins and alter the course of the disease. Among the additional cytogenetic defects, presence of Philadelphia [Ph] chromosome has rarely been documented in this subtype. Little is known about the consequences of its interactions with AML1-ETO, and its effect on morphological and clinical picture. Moreover, Ph[+] clones or subclones may appear at any point during the disease course. We herein report one such unusual case of a 26-year-old female, who was diagnosed to have t[8;21] and managed accordingly. During disease relapse after 2.5 years, the bone marrow showed extensive eosinophilia and basophilia. Subsequent molecular testing showed the presence of BCR-ABL in addition to the AML1-ETO fusion product