High glucose stress induces mesenchymal stromal cell senescence through up-regulating autophagy (LB842)

Diabetic hyperglycemia was reported to induce impairment of human bone marrow (BM) hematopoietic function and cause niche dysfunction. As multi-potent mesenchymal stromal cells (MSC) are a key constituent of BM hematopoietic niche, we determined the influence of high glucose (HG) on cultured MSCs. MSCs were cultured in medium containing 5.5 mM glucose (low glucose, LG) or 25 mM glucose (HG) for up to 28 days and cell proliferation and morphology were analyzed. MSCs cultured under HG exhibited reduced cumulative population doubling and BrdU incorporation and increased p16 and p21 in a time-dependent manner. Senescence-associated β-galactosidase (SA-β-Gal) positive cells and interleukin-6 (IL-6) production were increased. Cells underwent morphological changes consistent with senescence. Since cellular senescence is controlled by autophagy, we determined whether HG suppresses autophagy thereby inducing premature senescence. Interestingly, MSC cultured in HG medium exhibited enhancement of beclin-1 expression...