Adipose-derived Mesenchymal Stem Cells Stimulate Elastin Production by Adult Human Smooth Muscle Cells in a 3D Fibrin Scaffold

Adult human vascular smooth muscle cells (SMCs) do not normally produce elastin in-vivo, but do so in-vitro with treated with transforming growth factor beta-1 (TGF-β1). As human adipose-derived mesenchymal stem cells... [ view full abstract ]

Adult human vascular smooth muscle cells (SMCs) do not normally produce elastin in-vivo, but do so in-vitro with treated with transforming growth factor beta-1 (TGF-β1). As human adipose-derived mesenchymal stem cells (hADMSCs) are known to produce TGF-β1, we hypothesized that adult SMCs co-cultured with hADMSCs would produce elastin.

Constructs were made by embedding 6x104 commercially-sourced SMCs in fibrin gels. After two days, 9x105 commercially-sourced hADMSCs embedded in fibrin gels were added on top of the constructs. Additional experimental constructs were made without hADMSCs and treated with hADMSC conditioned media. Positive and negative control constructs lacking hADMSCs were treated with or without TGF-β1, respectively. After 28 days of culture, constructs were imaged with an Olympus multiphoton microscope to visualize elastin via autofluorescence.

The hADMSC/SMC co-culture experimental group produced a similar elastin network as the TGF-β1 treated positive controls. The conditioned media showed a less developed elastin network than the hADMSC/SMC co-culture group and positive control group. While the negative control did show elastin production in the ninhydrin assay, a developed elastin network was non-existent in the autofluorescent images.

The results of this study show promise for using hADMSCs as a possible elastogenic therapy, stimulating new elastin production by adult SMCs in vivo - ideally in the context of elastolytic diseases such as aneurysms. Interestingly, the underdeveloped elastin network seen in the conditioned media group may indicate that the co-culture of hADMSCs and SMCs allow the cells to communicate and better form an elastic network compared to growth factor treatment alone.