Impact of omega-3 fatty acids on expression of angiogenic cytokines and angiogenesis by adipose-derived stem cells.

Background And Aims: Human adipose-tissue derived stem cells (ADSC) are interesting novel targets in tissue engineering and regenerative medicine with pronounced angiogenic capacities. Furthermore, omega-3 fatty acids have been described to mediate cardioprotective effects, but their role in angiogenesis and vascular regeneration is not well-understood. Here, we analyzed the impact of different omega-3 fatty acids on angiogenesis by ADSCs.

Methods: Stem cells were cultured as monolayers or in 3D models, in spheroids embedded in collagen matrix or in co-cultures with human umbilical vein endothelial cells (HUVECs) in the Matrigel™ assay. The angiogenic properties of ADSCs were assessed by their sprouting and paracrine activities, gene expression by RT-PCR, Western blot, and enzyme immunoassay.

Results: Stimulation of undifferentiated ADSCs with docosahexaenoic acid (DHA) strongly upregulated angiopoietin-1 mRNA levels up to 4.6 ± 0.3 fold. Furthermore, Il-6 and Il-8 mRNAs were increased 4.2 ± 0.5 fold and 7.1 ± 1.1 fold, respectively. On the other hand, addition of DHA significantly decreased the cumulative sprout length by 2.7 ± 0.8 fold and reduced the total number of sprouts by 2.3 ± 0.9 fold in the in vitro angiogenesis assay. Moreover, excretion of IL-8 into the medium rapidly increased up to 1.7 ± 0.3 fold in response to treatment of ADSCs with DHA. Finally, protein kinase C inhibitor RO-31-8220 abrogated DHA-mediated up-regulation of angiopoietin-1 without significantly affecting ADSCs cell viability.

Conclusion: In conclusion, ADSCs might regulate the formation and function of microvascular networks.