[Viability and angiogenic activity of mesenchymal stromal cells from adipose tissue and bone marrow in hypoxia and inflammation in vitro].

Adult progenitor stromal cells derived from adipose tissue (ADSC) and bone marrow (BMDSC) hold great promise for use in cell-based therapy of ischemic diseases. Both cell lines secrete a various number of angiogenic cytokines which are regulated by hypoxia and improve vascularization of ischemic tissues being injected in damaged muscle or intravenously. However, such factors as low oxygen level and inflammation may impair the viability and functional activity of these cells after delivery to the ischemic area. We directly compared the reactions of ADSCs and BMDSCs to hypoxic and inflammatory conditions in vitro. Cultured ADSCs and BMDSCs from Balb/c mice were cultivated for 48 h under 1% O2 (hypoxia), 20% O2 (normoxia) or in the presence of inflammatory cytokines. Cell viability analyzed by annexin V-PE binding and 7AAD storage (flow cytometry), and by quantitative TUNEL showed no decrease under hypoxic condition. But cell apoptotic rates significantly increased (up to 70 %) under inflammatory condition. Inflammatory cytokines did not stimulate gene expression of angiogenic growth factors. Otherwise, gene expression profiles of angiogenesis-related cytokines showed activation of pro-angiogenic and suppression of anti-angiogenic factors in the cells under hypoxic condition. In general this effect was higher for ADSCs than for BMDSCs. Using in vitro and in vivo models of angiogenesis we have demonstrated that incubation under hypoxic condition increases stromal cells ability to stimulate blood vessels growth.