Avera Hair Vitality Peptide

Effects of MXD and Sh-Polypeptide 9 on tubulogenesis by HMVEC in monoculture or cocultured with FDPC

Background

Hair follicle (HF) growth requires interactions between epithelial and mesenchymal components and is regulated by angiogenic events driven by microvascular endothelium through the contribution of vascular endothelial growth factor (VEGF) 1-3. Several in vitro and in vivo techniques have been developed to promote hair reconstitution, but further studies are required for their clinical application in regenerative medicine and in particular for androgenetic alopecia (AGA) 4. The only approved topical medication for AGA to date is minoxidil (MXD) 5 that enhances dermal papilla vascularization via VEGF expression and plays a physiological role in maintaining a suitable HF blood supply6. Nonetheless, there is an increasing interest in more powerful and skin absorbable compounds for topic application. In vitro coculture systems can be successfully employed to test new promising drugs, and we recently established transwell-based cocultures to show that follicle dermal papilla cells (FDPC) promote survival, proliferation and tubulogenesis of human microvascular endothelial cells (HMVEC) 7. Here, we took advantage of this approach to compare the effects induced by MXD and Sh-Polypeptide 9, a VEGF-like synthetic biomimetic peptide capsulated by double-layered capsulation technology for better skin penetration. This strategy enhances the transdermal delivery efficacy, stability and purity of the active biomolecule.

Questions addressed

This study investigates the effects of Sh-Polypeptide 9, a VEGF-like biomimetic peptide, on paracrine interactions between endothelial cells and hair follicle papilla dermal cells. These data provide a mechanistic background for its potential use as a promoter of hair follicle vascularization.

Conclusions

We have recently shown that FDPC strongly support endothelial survival, proliferation and tubulogenesis in insert-based cocultures7.

Here, this approach was employed to investigate the activity of MXD and Sh-Polypeptide 9 (VEGF-like biomimetic peptide) on HMEC-FDPC crosstalk.

The results reveal that Sh-Polypeptide 9 promotes endothelial tubulogenesis and VEGF production more efficiently than MXD, in particular at low concentrations. In addition, the VEGF-like biomimetic peptide is more powerful on β-catenin expression by FDPC and on endothelial protection from oxidative stress.

In conclusion, our in vitro study points to Sh-Polypeptide 9 as a promising molecule; however, only further detailed mechanistic studies, together with ‘in vivo’ and clinical trials, will establish its positive effects against hair loss.

Results

Both MXD and Sh-polypeptide 9 were able to enhance HMVEC tubulogenic potential measured by endothelial tube formation assay both in terms of total tubule length and number of junctions. Interestingly, the presence of FDPC synergized with Sh-Polypeptide 9-induced tubulogenesis.