Carvacrol promotes angiogenic paracrine potential and endothelial differentiation of human mesenchymal stem cells at low concentrations

- Carvacrol promotes human mesenchymal stem cells viability, antioxidant activity and migration in vitro.
- Carvacrol stimulates trans‑differentiation of stem cells into endothelial lineage by inducing vWF and VE-cadherin.
- Angiocrine activity of stem cells is improved in the presence of Carvacrol by the secretion of VEGF.
- Condition media prepared from Carvacrol-exposed cells induce angiogenesis in vivo.

ObjectivesPhenolic monoterpene compound, named Carvacrol, has been found to exert different biological outcomes. It has been accepted that the angiogenic activity of human mesenchymal stem cells was crucial in the pursuit of appropriate regeneration. In the current experiment, we investigated the contribution of Carvacrol on the angiogenic behavior of primary human mesenchymal stem cells.MethodsMesenchymal stem cells were exposed to Carvacrol in a dose ranging from 25 to 200 μM for 48 h. We measured cell survival rate by MTT assay and migration rate by a scratch test. The oxidative status was monitored by measuring SOD, GPx activity. The endothelial differentiation was studied by evaluating the level of VE-cadherin and vWF by real-time PCR and ELISA analyses. The content of VEGF and tubulogenesis behavior was monitored in vitro. We also conducted Matrigel plug in vivo CAM assay to assess the angiogenic potential of conditioned media from human mesenchymal stem cells after exposure to Carvacrol.ResultsCarvacrol was able to increase mesenchymal stem cell survival and migration rate (p < 0.05). An increased activity of SOD was obtained while GPx activity unchanged or reduced. We confirmed the endothelial differentiation of stem cells by detecting vWF and VE-cadherin expression (p < 0.05). The VEGF expression was increased and mesenchymal stem cells conditioned media improved angiogenesis tube formation in vitro (p < 0.05). Moreover, histological analysis revealed an enhanced microvascular density at the site of Matrigel plug in CAM assay.ConclusionsOur data shed lights on the possibility of a Carvacrol to induce angiogenesis in human mesenchymal stem cells by modulating cell differentiation and paracrine angiogenic response.