Delle Monache Simona, Calgani Alessia, Sanità Patrizia, Zazzeroni Francesca, Gentile Warschauer Emilio, Giuliani Antonio, Amicucci Gianfranco, Angelucci Adriano
a Department of Biotechnological and Applied Clinical Sciences and.
b Division of Surgery , University of L'Aquila , L'Aquila , Italy.
Growth Factors. 2016 Aug;34(3-4):87-96. doi: 10.1080/08977194.2016.1191481. Epub 2016 Jun 30.
Recent studies suggest that adipose-derived stem cells (ASCs) play a role in tissue remodeling through the release of cytokines and growth factors. We compared the secreted cytokine profile of hypoxia-conditioned ASCs (hASCs) with normoxic ASCs (nASCs) and we analyzed the effect of ASCs conditioned medium (CM) on endothelial cells. We found that hypoxia induced a transient upregulation of VEGF in ASCs and a notable and enduring upregulation of leptin mRNA expression 30-fold greater than control after 24 h and up to 60-fold greater than control at day 7. CM from hASC stimulated EC tube formation to a significantly greater extent than CM from nASC. This might be due to leptin-secreted factor. Indeed, exogenous leptin stimulated the expression of HIF2-α, but not HIF1-α, and upregulated the expression of Flt-1 and Tie-1 proangiogenic receptors. In conclusion, hASCs may be particularly efficient in sustaining angiogenesis through the release of leptin.
最近的研究表明，脂肪来源的干细胞（ASC）通过释放细胞因子和生长因子在组织重塑中发挥作用。我们比较了缺氧条件下的ASC（hASC）与常氧ASC（nASC）分泌的细胞因子谱，并分析了ASC条件培养基（CM）对内皮细胞的影响。我们发现，缺氧诱导ASC中VEGF的短暂上调，以及瘦素mRNA表达在24小时后显著且持久地上调，比对照高30倍，在第7天比对照高60倍。hASC的CM比nASC的CM更显著地刺激内皮细胞形成管腔。这可能归因于瘦素分泌因子。事实上，外源性瘦素刺激HIF2-α的表达，但不刺激HIF1-α的表达，并上调促血管生成受体Flt-1和Tie-1的表达。总之，hASC可能通过释放瘦素在维持血管生成方面特别有效。
