Analysis of Bone Marrow-derived Mesenchymal Stem Cell Kinetics after Short-term Stimulation with Tumor Necrosis Factor-α (TNF-α)

Bone marrow-derived mesenchymal stem cells (BMSCs) have considerable potential for self-renewal and multi-differentiation. Tumor necrosis factor-α (TNF-α) is an inflammatory cytokine and is involved in tissue regeneration during wound healing. It was already reported that cultured human dental pulp cells acquire stem cell properties following short-term stimulation by TNF-α. However, it has not been clarified if BMSCs acquire stem cell properties after TNF-α treatment. The purpose of this study was to investigate the effect of short-term stimulation with TNF-α on BMSCs. Rat BMSCs were cultured up to 60% confluence and then incubated with 1–100 ng/ml of recombinant rat TNF-α (rTNF-α) for a further 2 days. After reaching subconfluence, cells were passaged once to remove rTNF-α completely before subsequent assays. Cells in the control group were passaged without stimulation. Expression levels of Nanog and Oct4 stem cell markers were significantly increased in the rTNF-α 10 ng/ml stimulation group. rTNF-α stimulation did not affect cell proliferation compared with the control group. However, rTNF-α stimulation led to a delay in cell differentiation. This study suggests that short-term TNF-α stimulation of BMSCs significantly increased their stem cell phenotype, but delayed their osteogenic cell differentiation.

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本論文は，著者Mio Naritaniの学位論文として提出され，学位審査・授与の対象となっている。