Hey all,
I came across this publication and thought it was worth sharing, it goes into detail about how the search for hair growth drugs can be hindered by the lack of into vitro models and provides the mode below:
Extract:
"The search for hair growth drugs is hindered by the lack of in vitro models which adequately mimic the native hair follicle.1 The in vitro organotypic model accurately reproduces hair drug responses from the hair shaft elongation of cultured hair follicles; however, these can only be maintained for 2 weeks, posing a challenge to obtain sufficient samples for comprehensive and continuous studies.2
In a recent issue of this journal, Paik et al. report an optimized method for testing hair growth reconstitution capacity, using both mouse dermal and epidermal cells.3 In this work, they embedded mouse dermal cells in type I collagen (3D) and overlaid them with mouse epidermal cells, then grafted the composites onto nude mice. A negative control was also prepared, where the dermal cells were precultured on a 2D plate. Their 3D assay regenerated hair follicles, while the negative control did not. When Wnt3 was added, the number of regenerated hairs increased, suggesting use of the approach for the testing of hair drugs.
The question that begs an answer is whether reproducing epithelial–mesenchymal (EM) interactions is actually required for in vitro hair drug testing. In our work as well as that of others, co‐cultures of dermal papilla (DP) and keratinocytes have been used to recapitulate such interactions and thus simulate the response of native hair follicles when exposed to hair drugs [s1].4, 5 But is it the 3D nature of such co‐cultures or the EM interactions which govern the response? Paik et al3 showed that levels of hair‐inducing marker genes were increased in their 3D skin equivalent compared to the 2D model. Yet others have also shown that 3D co‐culture of DP spheroids alone can enhance the expression of these markers [s2–s6] If the epithelial cells could be dispensed with in such models, this would allow for quick and efficient first‐pass screening of hair drug candidates.
To shed light on this issue, we developed a technique to obtain uniform DP microtissues with controllable size, by culturing DP cells in PDMS moulds, whereupon they aggregated to form spheroids within 24 hours. DP microtissues were collected and their expression levels characterized for a list of 126 signature DP genes. It was observed that all 126 genes were expressed by the DP aggregates, with 104 genes upregulated (fold change >1.5) as compared to 2D‐cultured DP cells. In particular, genes which are involved in FGF, WNT and BMP signalling pathways were upregulated (i.e. FGF7, SPRY1, BMP2, SOSTDC1, WNT5A, NDP, WIF1 and LEF1). These are critical pathways which have been reported to be important for the maintenance of intrinsic properties of DP cells [s7]. Other upregulated genes included HEY1, VCAN, WIF1 and SOSTDC1, which are genes that have been associated with the DP molecular signature [s8].
We then went on to investigate the effect of hair growth‐controlling drugs on the DP microtissues. Figure 1 shows the gene expression levels of treated DP microtissues for a selection of anagen and catagen genes, grouped into those which are involved in the anagen stage: FGF7, WNT5A, VEGF and catagen stage: BMP4, FGF5 and TGFβ2 [s9]. Our screening assay could demonstrate the catagen inducing effect of dexamethasone and the anagen‐inducing effect of cyclosporin A, minoxidil and bimatoprost. Thus, while our results in no way suggest that a DP model alone is sufficient to examine mechanisms underlying epithelial–mesenchymal interactions, they indicate the potential of the model for the screening of molecules that influence hair growth."
Whilst this isn't a new drug it does provide a new means of screening molecules that influence hair growth, hopefully this speeds up the pre-clinical development for newer drugs. Something cool is I was also unaware that Bimatoprosts effect on FGF7 is superior to Minoxidil.
Publication Source:
onlinelibrary.wiley.com
I came across this publication and thought it was worth sharing, it goes into detail about how the search for hair growth drugs can be hindered by the lack of into vitro models and provides the mode below:
Extract:
"The search for hair growth drugs is hindered by the lack of in vitro models which adequately mimic the native hair follicle.1 The in vitro organotypic model accurately reproduces hair drug responses from the hair shaft elongation of cultured hair follicles; however, these can only be maintained for 2 weeks, posing a challenge to obtain sufficient samples for comprehensive and continuous studies.2
In a recent issue of this journal, Paik et al. report an optimized method for testing hair growth reconstitution capacity, using both mouse dermal and epidermal cells.3 In this work, they embedded mouse dermal cells in type I collagen (3D) and overlaid them with mouse epidermal cells, then grafted the composites onto nude mice. A negative control was also prepared, where the dermal cells were precultured on a 2D plate. Their 3D assay regenerated hair follicles, while the negative control did not. When Wnt3 was added, the number of regenerated hairs increased, suggesting use of the approach for the testing of hair drugs.
The question that begs an answer is whether reproducing epithelial–mesenchymal (EM) interactions is actually required for in vitro hair drug testing. In our work as well as that of others, co‐cultures of dermal papilla (DP) and keratinocytes have been used to recapitulate such interactions and thus simulate the response of native hair follicles when exposed to hair drugs [s1].4, 5 But is it the 3D nature of such co‐cultures or the EM interactions which govern the response? Paik et al3 showed that levels of hair‐inducing marker genes were increased in their 3D skin equivalent compared to the 2D model. Yet others have also shown that 3D co‐culture of DP spheroids alone can enhance the expression of these markers [s2–s6] If the epithelial cells could be dispensed with in such models, this would allow for quick and efficient first‐pass screening of hair drug candidates.
To shed light on this issue, we developed a technique to obtain uniform DP microtissues with controllable size, by culturing DP cells in PDMS moulds, whereupon they aggregated to form spheroids within 24 hours. DP microtissues were collected and their expression levels characterized for a list of 126 signature DP genes. It was observed that all 126 genes were expressed by the DP aggregates, with 104 genes upregulated (fold change >1.5) as compared to 2D‐cultured DP cells. In particular, genes which are involved in FGF, WNT and BMP signalling pathways were upregulated (i.e. FGF7, SPRY1, BMP2, SOSTDC1, WNT5A, NDP, WIF1 and LEF1). These are critical pathways which have been reported to be important for the maintenance of intrinsic properties of DP cells [s7]. Other upregulated genes included HEY1, VCAN, WIF1 and SOSTDC1, which are genes that have been associated with the DP molecular signature [s8].
We then went on to investigate the effect of hair growth‐controlling drugs on the DP microtissues. Figure 1 shows the gene expression levels of treated DP microtissues for a selection of anagen and catagen genes, grouped into those which are involved in the anagen stage: FGF7, WNT5A, VEGF and catagen stage: BMP4, FGF5 and TGFβ2 [s9]. Our screening assay could demonstrate the catagen inducing effect of dexamethasone and the anagen‐inducing effect of cyclosporin A, minoxidil and bimatoprost. Thus, while our results in no way suggest that a DP model alone is sufficient to examine mechanisms underlying epithelial–mesenchymal interactions, they indicate the potential of the model for the screening of molecules that influence hair growth."
Whilst this isn't a new drug it does provide a new means of screening molecules that influence hair growth, hopefully this speeds up the pre-clinical development for newer drugs. Something cool is I was also unaware that Bimatoprosts effect on FGF7 is superior to Minoxidil.
Publication Source: