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.
Long-lost dead hair follicles can certainly regenerate under the right circumstances. Unfortunately, one potential side effect of such future treatments is unimpeded cell growth proliferation that could lead to cancer. Hence the need for lengthy human clinical trials.
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.
Note that transforming growth factor beta (TGF-β) is one of the growth factors in PRP.
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.
TGF-β family and the hair growth cycle. Source: IOSR Journal of Dental and Medical Sciences. Author: Xiuhong Jiao.
I last updated my main platelet-rich plasma post (does PRP work for hair loss) in 2020. In there, I list over 50 studies that support the benefits of PRP scalp injections for hair growth.
I have written many other posts on platelet-rich plasma. Among the highlights include: a summary of key growth factors in PRP; rare instances of hair darkening; and Dr. John Cole’s interesting experiments with activated and sonicated PRP.
However, most readers are justifiably very skeptical about platelet-rich plasma. We see very few positive testimonials and reviews on hair loss forums, while studies suggest otherwise. One possible reason is that the methods used for PRP treatments are all over the place and impact success rates significantly.
Doctors who are totally inexperienced with hair loss treatments often start injecting PRP into patient scalps without any training. Many use the cheapest possible centrifuges and never even try to measure platelet counts.
In this post, I attempt to describe platelet-rich plasma treatment methodologies used by various leading hair transplant surgeons. Note that some physicians often combine PRP treatments with one or more of: ACell, exosomes and microneedling.
Update: December 2022
Two patients in Croatia got great platelet-rich plasma hair growth results via a novel protocol. Make sure to check out both the before and after photos. Each received an initial injection that contained a large volume of concentrated PRP (cPRP) solution activated by calcium (via the Arthrex Angel System). this was followed by a second, small-volume booster without activation. The Arthrex Angel System achieves a high concentration of thrombocyte cells.
PRP Hair Growth Treatment: Platelets per Microliter
Perhaps the most experienced doctor in the US when it comes to using platelet-rich plasma for hair growth is Dr. Joseph Greco. I have covered him a few times. Besides using PRP, he also uses a purified version of PRP called CRP (Cytokine Rich Plasma). See this chart on his site for a comparison of differences between the two.
Dr. John Cole who I mentioned earlier is also among the most experienced American physicians when it comes to using PRP for hair growth. Dr. Cole also uses CRP. On his site, he has a very interesting article section titled “Dr. Cole discusses differences in PRP.” He notes that most PRP kits in use today lack when it comes to ultimate platelet concentrations and platelet yields. In his opinion, the best benefit for hair growth comes at platelet-rich plasma concentration levels of 1 million platelets per milliliter.
Dr. Cole uses a Hemoccult machine that uses light to differentiate cells and quantify them accurately. One interesting thing that Dr. Cole told me was that “What I can tell you for sure on platelet-rich plasma is that you want a reddish PRP. Not a yellow PRP. The best and youngest platelets are on the surface of the red cells. Hence, you want a little flash of red in the final spin to capture those platelets.”
Dr. Joseph Yaker shared with me an interesting series of slides he made for a presentation on the need to standardize PRP dosing. Since 2018, he has been using the TruDose™ system at his practice for platelet-rich plasma dosing accuracy. Dr. Yaker offers his own version of platelet-rich plasma called Precision PRP™️.
PRP hair loss treatment using the TruDose™ system.
The foremost expert on platelet-rich plasma for hair growth in the world might be Dr. Pietro Gentile from Italy. Especially when it comes to number of study publications. Dr. Yaker in his aforementioned slides mentioned a 2015 study from Dr. Pietro Gentile that found an ideal PRP dosage of 1.5 million platelets per microliter. The exact quote from this study:
“A mean of 1,484,555.6 platelets per microliter in the PRP preparation could effectively stimulate follicular and perifollicular angiogenesis (blood vessel formation), which is suggested to be one of the major factors in active hair growth.”
Another leading US based hair transplant surgeon Dr. Aron Nusbaum published a study in 2018 titled: “Examining the Variability of PRP with Different Preparation Systems.” Him and his partner found that the concentration of platelets produced by four different commercially available systems demonstrated wide variance. Also, while most systems only require blood collection of 15-22cc, the Arthrex System uses over 120ml of blood. Dr. Nusbaum told me that his clinic uses the Angel System by Arthrex. They found this device leads to the highest platelet concentration. He also adds ACell during the procedure, and they recommend PRP treatments every 6 months.
Dr. Jerry Cooley is yet another highly experienced platelet-rich user. In one of his past comments he stated the following:
“There a lot of different ways to ‘do’ PRP. Adding ACell is just one variable. Some of these other variables are: the device used to centrifuge the blood; the concentration of platelets achieved; the total volume injected; the size of the syringe and needle used to do the injecting; the depth level in the scalp it is injected; whether the PRP is ‘activated’ or not; the use of microneedling; etc. All of these can affect the result in my opinion.”
Make sure to see Hair Transplant Mentor Joe Tillman’s video of his platelet-rich plasma treatment with Dr. Cooley in 2016.
Activated versus Non-Activated
Many researchers recommend differentiating between autologous activated versus non-activated platelet-rich plasma. The former entails “activation” to induce growth factor secretion via the addition of calcium gluconate (or sometimes calcium chloride or thrombin). In the above video, Dr. Cooley injects calcium thrombin during the activation process.
A new January 2022 paper titled “Lasers, lights, and compounds for hair loss in aesthetics” contains a detailed section on platelet-rich plasma. It includes a discussion of autologous activated PRP (AA-PRP) versus non-activated autologous PRP (NA-PRP). The full version of the paper can be read via Sci-Hub (whose link keeps changing, so I am not posting here).
Among the most relevant quotes in this paper:
“The number of centrifugations, revolutionary speed, and spin time can affect platelet activity, degranulation, and growth factor viability. For example, longer or faster spin cycles more effectively separate the erythrocytes, buffy coat, and plasma, but this may also damage platelets and cause premature release of growth factors.”
“Preparation parameters should include the presence or absence of an anticoagulant, volume of blood drawn, presence or absence of leukocytes, spin method (speed and duration), activator used, and fraction of plasma collected. Authors should also report the mean platelet concentration, total volume, and volume per area used in treatment. This level of detail will allow for improved standardization that can be applied to real-world dermatology practice.”
Leukocytes and Fibrin Matrix
A proposed classification system that the above paper outlines would break out platelet-rich plasma into five categories:
