Abstract

In adult organisms, stem cells, found primarily in the bone marrow and in low numbers in other organs, are mobilized to the injured tissue where they participate in the repair process. Stromal cell-derived factor -1a (SDF-1a) is critical for stem cell trafficking during injury. Very little is known about how nutrition affects this process. Our objectives were to determine how Glutathione (GSH) depletion, observed with aging and in numerous chronic disease states, affects the functional response of bone marrow cells to SDF-1a. Bone marrow stem cells (BMSC) from 8 week old C57BL/6J mice were isolated, and were cultured for 24 hours in buthionine sulfoximine (BSO), an inhibitor of GSH synthesis. SDF-1a (120 ng/ml) dependent chemotaxis was determined in viable cells, over 3 hours, using a modified Boyden chamber method. We found a 5 fold decline in migration, in cells depleted of GSH compared to control. Our data show that GSH is important in the directional migration of BMSC to SDF-1a and indicate that signal transduction pathways initiated by SDF-1a may be redox sensitive. Therefore, in states of chronic oxidative imbalance, stem cell response to SDF-1a may be attenuated slowing tissue regeneration and repair. As nutrition can impact levels of GSH, dietary control of antioxidant status may provide an opportunity to enhance repair and improve recovery in patients with injury.

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