Melatonin finely tunes proliferation and senescence in hematopoietic stem cells

Abstract

Human hematopoietic stem/progenitor cells (HSPCs) are pluripotent cells that gradually lose their self-renewal and regenerative potential, to give rise to mature cells of the hematopoietic system by differentiation. HSPC infusion is used to restore hematopoietic function in patients with a variety of onco-hematologic and immune-mediated disorders. The functionality of these cells is therefore of great importance to ensure the homeostasis of the hematopoietic system. Melatonin plays an important role as immunomodulatory and oncostatic hormone. In the present manuscript, we aimed at evaluating the activity of melatonin in modulating HSPC senescence, in the attempt to improve their hemopoietic regenerative potential. We exposed HSPCs to melatonin, in different conditions, and then analyzed the expression of genes regulating cell cycle and cell senescence. Moreover, we assessed cell senescence by β-galactosidase and telomerase activity. Our results showed the ability of melatonin to counteract HSPC senescence, thus paving the way for enhanced efficiency in their clinical application.

Keywords: Cell senescence; Cellular mechanisms; Gene expression; Hematopoietic stem cells; Melatonin; Oxidative stress; Regenerative medicine.