Combined pre-conditioning with salidroside and hypoxia improves proliferation, migration and stress tolerance of adipose-derived stem cells

Oxidative stress after ischaemia impairs the function of transplanted stem cells. Increasing evidence has suggested that either salidroside (SAL) or hypoxia regulates growth of stem cells. However, the role of SAL in regulating function of hypoxia-pre-conditioned stem cells remains elusive. Thus, this study aimed to determine the effect of SAL and hypoxia pre-conditionings on the proliferation, migration and tolerance against oxidative stress in rat adipose-derived stem cells (rASCs). rASCs treated with SAL under normoxia (20% O₂ ) or hypoxia (5% O₂ ) were analysed for the cell viability, proliferation, migration and resistance against H₂ O₂ -induced oxidative stress. In addition, the activation of Akt, Erk1/2, LC3, NF-κB and apoptosis-associated pathways was assayed by Western blot. The results showed that SAL and hypoxia treatments synergistically enhanced the viability (fold) and proliferation of rASCs under non-stressed conditions in association with increased autophagic flux and activation of Akt, Erk1/2 and LC3. H₂ O₂ -induced oxidative stress, cytotoxicity, apoptosis, autophagic cell death and NF-κB activation were inhibited by SAL or hypoxia, and further attenuated by the combined SAL and hypoxia pre-treatment. The SAL and hypoxia pre-treatment also enhanced the proliferation and migration of rASCs under oxidative stress in association with Akt and Erk1/2 activation; however, the combined pre-treatment exhibited a more profound enhancement in the migration than proliferation. Our data suggest that SAL combined with hypoxia pre-conditioning may enhance the therapeutic capacity of ASCs in post-ischaemic repair.

Keywords: adipose-derived stem cells; hypoxia; oxidative stress; salidroside; stem cell function.