Design of In Vitro Hair Follicles for Different Applications in the Treatment of Alopecia—A Review

Abstract

The hair research field has seen great improvement in recent decades, with in vitro hair follicle (HF) models being extensively developed. However, due to the cellular complexity and number of various molecular interactions that must be coordinated, a fully functional in vitro model of HFs remains elusive. The most common bioengineering approach to grow HFs in vitro is to manipulate their features on cellular and molecular levels, with dermal papilla cells being the main focus. In this study, we focus on providing a better understanding of HFs in general and how they behave in vitro. The first part of the review presents skin morphology with an emphasis on HFs and hair loss. The remainder of the paper evaluates cells, materials, and methods of in vitro growth of HFs. Lastly, in vitro models and assays for evaluating the effects of active compounds on alopecia and hair growth are presented, with the final emphasis on applications of in vitro HFs in hair transplantation. Since the growth of in vitro HFs is a complicated procedure, there is still a great number of unanswered questions aimed at understanding the long-term cycling of HFs without losing inductivity. Incorporating other regions of HFs that lead to the successful formation of different hair classes remains a difficult challenge.

Tissue Engineering and Regeneration of the Human Hair Follicle in Androgenetic Alopecia: Literature Review

“…The dermal papilla (DP) expresses versican mostly in the anagen stage, with a decreased expression in the catagen stage, and is nondetectable in telogen, indicating its importance in the process of maintaining normal HF growth. Patients affected by male AGA were found to have little-to-no versican expression in the DP [13,14].…”

“…The final step in both approaches is to combine the epithelial and mesenchymal components and form engineered instructive minibulbs capable of generating mature and functional HFs once transplanted into the recipient's skin (Figure 2) [8]. In addition, the aims of generating HFs through TE also include their application in the research and clinical field, such as their use in hair transplantation procedures and pharmacological tests [13].…”

“…Modulation of the JAK-STAT signalling pathway has also been shown to increase the inductive capacity of DPC cultures [50]. The problem with 2D monolayer HF models is that they do not reproduce several key features of the HF microenvironment and DPCs rapidly lose their inductivity in culture [13,39]. Probably the most effective culture technique to reproduce the native trichogenicity of DP is the establishment of three-dimensional (3D) sphere cultures [8,51].…”

“…Three-dimensional Spheroid culture helps DPCs to aggregate and engage in cell-cell contacts, a crucial feature of HF in vivo [39]. Thus, one should try to obtain in vitro a cell structural arrangement as close as possible to the in vivo reality, with seeding of DPCs in wells being very useful [13]. Three-dimensional cultures have been shown to display expression of specific markers of HF induction, unlike 2D cultures [13].…”

In Vitro Hair Growth Promoting Effect of a Noncrosslinked Hyaluronic Acid in Human Dermal Papilla Cells

“…However, there are some limitations related to the method as the invasive procedure, the limited number of follicles extracted, and the short time to be cultured and maintained ex vivo. As recently summarized by Znidaric and his team, monolayer cultures of specific cell types with a role in hair follicle morphogenesis and hair growth cycles, as dermal papilla cells (DPCs), can be used as a valid alternative [ 13 ]. DPCs were selected to demonstrate the hair growth modulating effects of several growth factors, cytokines, and herbal products, analyzing different key biomarkers of cell proliferation, apoptosis, and analysis of growth factors.…”