Question: 

Adipose-derived stem cells (ADSCs) are interesting novel targets in tissue engineering and regenerative medicine. The ADSCs have been shown to promote tissue regeneration by secretion of angiogenic cytokines and growth factors. Whether ADSCs are able to support the sprouting of new blood vessels in angiogenesis and vascular regeneration is not well understood. Furthermore, omega-3 fatty acids have been described to promote vasoprotection. However, their role in angiogenesis and vascular regeneration is not known.

Methods and Results: 

We analyzed the impact of different polyunsaturated fatty acids on the angiogenic properties of ADSCs. Stem cells were cultured as monolayers or in spheroids surrounded by a collagen matrix. The angiogenic potential of ADSCs was evaluated by their sprouting activity. Exposure of ADSCs spheroids to 50 mM docosahexaenoic acid (DHA) for 24 h significantly decreased the cumulative sprout length and the total number of sprouts from the spheroids. In contrast, incubation with the same amount of eicosapentaenoic (EPA), myristic, elaidic, oleic, alpha-linoleic and linoleic acids did not affect sprouting of ADSCs in spheroids. Furthermore, treatment of monolayers of ADSCs with either DHA or EPA increased VEGF-A and angiopoetin-1 expression as analysed by quantitative RT-PCR. Exposure of cells to 1% oxygen (hypoxic conditions) potentiated this effect. In co-cultures of ASDC with human umbilical vein endothelial cells (HUVECs) in a three-dimensional in vitro Matrigel assay, ADSCs localized at the outer surface of the branching points formed by capillary-like endothelial networks.

Conclusions: 

Our data suggest a supportive role of adipose-derived stem cells in the formation of vascular networks. Omega-3 fatty acids reduced sprouting in vitro, but induced angiopoietin-1 in adipose-derived stem cells. This novel mechanism might increase vascular stability.