This past month was the most important one of the year in the hair loss world. First came the major finding of SCUBE3 signaling and hair growth from researchers at the University of California, Irvine (UCI). Several weeks later, a team from the University of California, Riverside (UCR) released findings that TGF-β is the key protein that governs hair follicle growth and death.
A lot of people confused the above two studies. For one, those two universities are less than one hour drive from each other. Also, in the SCUBE3 study, there was a connection made with TGF-β (aka TGF Beta).
Interestingly, the lead authors of the above two studies (Wang and Plikus) even collaborated in a 2017 study relating to hair growth pattern differences around the body.
Key quote from study co-author and mathematical biologist Dr. Quixuan Wang:
TGF-beta has two opposite roles. It helps activate some hair follicle cells to produce new life, and later, it helps orchestrate apoptosis, the process of cell death.
Also according to Dr. Wang: When a hair follicle kills itself, it never kills its stem cell reservoir. If the surviving stem cells receive the signal to regenerate, they can divide and develop into a new follicle. I am sure we have heard something similar many times in the past.
For some reason, TGF-β is called a chemical rather than protein (or cytokine) in most of the articles and headings. The UCR researchers found that when the TGF-β chemical is in high concentration levels, it kills hair follicles. However, when the levels are “just right“, it causes them to grow new hairs.
If the levels of TGF-Beta can be controlled, it will be possible to prevent chemical buildup and further hair loss. In a best case scenario, it might also be possible to re-activate follicle stem cells and stimulate hair regrowth.
Will these Mathematicians cure hair loss? I certainly hope so, since I have a bias towards the subject as a past Math major.
TGF Beta 1, 2 and 3
Note that there are three different isoforms of transforming growth factor beta (TGF-β) in mammals:
TGF beta 1.
TGF beta 2.
TGF beta 3.
A 2019 study from China titled: “New Insight into the Relationship between TGF-β Superfamily and Noggin in hair cycle” contains a great diagram and table that explains the impact of each of the three on the hair growth cycle. I am pasting it below.
I have mentioned platelet-rich plasma (PRP) in a dozen or so posts on this blog over the past three years. The positive effect of PRP on hair growth is somewhat controversial. However, there is no controversy when it comes to the fact that PRP contains numerous concentrated growth factors (GFs). And many of these growth factors are known to at least modestly benefit hair thickness as well as hair quantity.
In the past I have briefly discussed some of the key growth factors that are highly concentrated in PRP. I think it is worth having a separate post here that discusses all of them in a bit more detail. There is a good chance that I am still missing things, so any corrections and suggestions are welcome via the comments.
It should be noted that even many non-PRP related hair loss products target one or more of the below listed growth factors in order to stimulate hair growth. There is a good chance that both PRP as well as hair loss products that contain some of the below growth factors make existing hair stronger. However, it is unlikely that such products ever bring back hair that has been lost for a long time.
Growth Factors in Platelet-Rich Plasma
The key growth factors in PRP treatment that are supposedly beneficial to hair growth are:
Adipose-derived stem cells (ADSCs — an exciting recent development in the hair loss world) are rich in various growth factors, including IGF-1.
Last year, an important and widely publicized study found that topical application of oleuropein (derived from the leaves of olive drupes) induces hair growth in mice. According to the study findings, oleuropein-treated mouse skin showed substantial upregulation of IGF-1.
I list fibroblast growth factor (FGF) next because I have also covered it many times on this blog before. There are 22 types of FGFs numbered FGF-1 through FGF-22. A significant number of these influence hair growth. I may write an entire detailed post on FGFs at some point in the future. I have covered some of the key ones on this blog before, in particular FGF-5, which discourages hair growth and has to be inhibited. Australian company Cellmid’s Evolis line of products claims to inhibit FGF-5.
Note that PRP does not inhibit growth factors. So it is more relevant for the purposes of this post to discuss some of the FGFs that promote hair growth. It seems like the main ones are FGF-1, FGF-2, FGF-7, FGF-9 and FGF-10. Evidence for three of those (FGF-1, FGF-2 and FGF-10) and their positive effects on hair is found in an important 2014 study from China. Fibroblast growth factors stimulate hair growth through β-Catenin and Shh expression.
Note that “hair cell regeneration” or variations of that term are mentioned a number of times in this study, even if in mice. PRP is said to increase FGF-2 concentration levels. Interestingly, when I interviewed Dr. Malcolm Xing last year, he mentioned that FGF-2 is the preferred growth factor used at this clinic for his work purposes.
Finally, FGF-7 (also called keratinocyte growth factor, or KGF) is required for hair growth. The well known researcher Dr. Elaine Fuchs co-authored an important study on FGF-7, hair development and wound healing all the way back in 1995. Moreover, Histogen’s Hair Stimulating Complex product is focusing on KGF as one of the key growth factors to be injected in human scalps.
Besides hair growth, vascular endothelial growth factor (VEGF) is also involved in blood vessel formation. A 2001 study concluded that “normal hair growth and size are dependent on VEGF-induced perifollicular angiogenesis”. Note that Shiseido’s adenosine based shampoo also promotes the expression of VEGF. The previously discussed adipose-derived stem cells are also rich in various growth factors including VEGF.
A number of studies have examined natural and synthetic products that increase VEGF and their impact on scalp hair. For example, in 2018, Japanese researchers found that water-soluble chicken egg yolk peptides stimulate hair growth through induction of VEGF production.
Transforming growth factor beta (TGF-β) is a cytokine protein growth factor. From the brief research I did, it seems like TGF-β actually adversely impacts hair growth! e.g., see here, here and here. So I am not sure if this growth factor in PRP benefits hair. Will update this if I find out more.