Category Archives: PRP

Key Growth Factors in Platelet-Rich Plasma

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.

PRP Growth Factors
Platelet-Rich Plasma (PRP) Growth Factors.

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. It is probably 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 that are supposedly beneficial to hair growth are:

  • Insulin-Like Growth Factor 1 (IGF-1).
  • Fibroblast Growth Factor (FGF).
  • Platelet-Derived Growth Factor (PDGF).
  • Vascular Endothelial Growth Factor (VEGF).
  • Epidermal Growth Factor (EGF).
  • Transforming Growth Factor Beta (TGF-β).
  • Nerve Growth Factor (NGF).

IGF-1

I start with the growth hormone insulin-like growth factor 1 (IGF-1) because I have already covered it a few times before.

  • Promotion of IGF-1 expression is one of the main considerations behind Shiseido’s bestselling adenosine based products.
  • US-based Follicept was targeting IGF-1 delivery in its hair loss product, prior to the company’s demise.
  • 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.

FGF

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.

FGF-9 has become an especially important growth factor in large part due to the work of the renowned Dr. George Cotsarelis, who holds a patent titled “Fibroblast growth factor-9 promotes hair follicle regeneration after wounding“. Dr. Cotsarelis is also a co-author of a 2013 paper that concludes: “The importance of FGF-9 in hair follicle regeneration suggests that it could be used therapeutically in humans“.

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.

PDGF

Platelet-derived growth factor (PDGF) is a key growth factor involved in blood vessel formation. A 2006 study from Japan found that “PDGF isoforms induce and maintain anagen phase of murine hair follicles“. Adipose-derived stem cells (ADSCs) are rich in various growth factors, including  PDGF, and are increasingly utilized in the hair loss world.

VEGF

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.

Also, one of the ways in which Minoxidil works to grow hair is via the upregulation of VEGF. Moreover, Histogen’s Hair Stimulating Complex product is focusing on VEGF as one of the key growth factors to be injected in human scalps.

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.

EGF

Epidermal growth factor (EGF) promotes cell growth, proliferation and differentiation. A 2003 study from Hong Kong concluded that EGF functions as a biological switch that is “turned on and off in hair follicles at the beginning and end of the anagen phase of the hair cycle“.

TGF-β

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.

NGF

There seem to be mixed opinions on the impact of nerve growth factor (NGF) on the hair cycle in any significant manner. A 2006 study suggests both anagen-promoting and catagen-promoting effects of NGF on the hair cycle. Another study, also from 2006, seems to also find different effects of NGF on the hair cycle.

Dr. John Cole’s Interesting New Study on PRP

US (Atlanta, Georgia) based Dr. John Cole is one of the world’s most respected hair transplant surgeons. He has trained numerous other surgeons around the world over the years, and is almost certainly among the world’s five most experienced surgeons when it comes to the now dominant follicular unit extraction (FUE) method of hair transplantation. In 2013, Dr. Cole received the prestigious ISHRS Golden Follicle award.

More importantly, over the years Dr. Cole has been at the forefront of testing out new procedures and techniques, and at adding his own cutting edge modifications to existing procedures. Some might consider a lot of these modifications to just be marketing gimmicks, but I think it is genuine interest on the part of Dr. Cole to improve the overall field of hair restoration.

In recent months, Dr. Cole has taken an active interest in improving the platelet-rich plasma (PRP) procedure. I discussed PRP for hair loss in numerous posts. PRP for hair growth has taken off like wildfire in the past few years, but results have been extremely inconsistent. Moreover, almost all hair transplant surgeons who offer PRP (often supplemented with ACell) treatments agree that patients will not regrow hair on totally bald areas of their scalps.

Nevertheless, many claim that PRP usually makes existing hair thicker and even regrows recently shrunken or telogen hair. I am a bit skeptical of the latter, but not entirely dismissive. Over the years I have read a few positive testimonials about PRP on hair loss forums from respectable long-term members. However, none of these testimonials have suggested any miracle results.

Dr. John Cole’s New PRP Study

This week Dr. Cole sent me an interesting e-mail about his thoughts on PRP and about his new study on PRP and I have pasted the contents of his e-mail below. Note that I had not e-mailed him to ask anything about PRP, so this e-mail was Dr. Cole’s own initiative. I have added some brief notes in red below and bolded some of the important parts of Dr. Cole’s e-mail.

I am curious to see what blog readers think. As always, please try to stick to intelligent blog post related comments with no insults. Unrelated comments about interesting new developments in the hair loss world are ok.

Here is the current PRP study I am proposing. We have seen a 50% increase in hair density at six months with Angel PRP (see here) and a decrease with Regen PRP (see here) at that point, but there is an improvement in density and hair check at 12 months with both. That’s good. An increase in hair density is not enough. We need an increase in hair mass and hair check shows we can get this. It just proves that not all PRP is equal. Some are terrible.

What we found with Regen PRP was that some growth factor concentrations were quite low. It suggests that some PRP kits produce better quality platelets because overall levels of platelets were similar. By the way, 1X levels of platelets just don’t work (I have read that 5X is the desired number). Don’t waste your time, nor you money on those. What we have not documented to date is a benefit from Acell (FYI — there are other extracellular matrix products out there too besides ACell), but our data is incomplete at this point, so

I’m holding back on any conclusions on Acell. What I think Acell does with PRP is prolong the duration of growth factors by allowing a sustained release. The problem with Acell is that it is of porcine origin, which makes it intolerant to some religious affiliations.

Thus we need to evaluate the benefits of microparticles such as dalteparin and protamine on the advantages of a sustained release of growth factors at some point soon. These much less expensive adjuncts to PRP would remove religious barriers, as well as, remove financial burden to patients.

We know that Acell can help with follicle regeneration since we cannot locate up to 48% of FUE extraction sites (he is talking about hair transplant extraction here) when we apply it, but whether Acell stimulates stem cells in follicles in conjunction with PRP remains a mystery that we will solve soon. For now, we have to focus on higher growth factor concentrations obtained by sonicated PRP.

Accordingly, now we want to focus on sonicated PRP. At 3 1/2 months, I have found 64 out of 80 grafts growing. That’s amazing with sonicated PRP. The growth factor concentrations in sonicated PRP are off the chart high. As a result, we are engaging in a study in collaboration with the department of chemical engineering at the University of Michigan to investigate the effect of high concentrations of growth factors on the dermal papilla this year.

We also want to look at the density of hair and the hair check and the diameter in a comparison of standard PRP with Acell and sonicated PRP with Acell.

I want to emphasize that across the board all patients in our study done in conjunction with Chiara Insalaco, a plastic surgeon from Rome, had an initial decrease in hair density and hair mass (Hair Check). This reduction in density and hair mass mimics the effect we see from Minoxidil.

I speculate that all patients undergo a transformation from the telogen (resting) phase to the anagen (growing phase) with high quality, concentrated PRP. Anagen effluvium leads to an initial period of shedding, which means that patients get worse before they get better. Just as an adult tooth pushes the baby tooth out of the way, the anagen hair pushes the telogen hair out of the way.

We noted this right away with hair clippings. We found that the percentage of shorter hairs was much higher following treatment with PRP, and the proportion of longer hairs was much lower following PRP. Over time both density and length increase, which leads to an increase in hair mass closer to 12 months following treatment with PRP. Dr. Insalaco and I counted every hair that we clipped in the study area and grouped them by length.

Following PRP, the number of longer hairs drops. However, it recovers and exceeds the number of pre-treatment long hairs following the injection of PRP. Based on these findings, I would recommend a high-quality PRP every 6 to 12 months as a maintenance treatment; however, the duration of this benefit remains unknown.

What PRP will not do is to improve the quality of miniaturized hair for the most part based on our global photography. Years ago in 1999, I found that the last thing lost as follicular unit density, while the first thing lost was hair density in androgenic alopecia (confusing sentence). The prompted me to recommend the use of retardants to hair loss early on before the loss of follicles. My conclusions were antecedent to those later proposed by pharmaceutical companies and other researchers.

There are no means to bring follicles back once lost (I think there are rare cases where you can bring back long gone hair), and PRP fails in this objective too. However, unlike products that retard the formation of DHT, PRP carries no unpleasant side effects such as a persistent loss of libido and depression (I do not buy the theory that DHT inhibitors causes depression — maybe depression due to other side effects). As such, PRP seems to be highly preferable to the use of chemicals that can cause long-standing physiological consequences.

We are fortunate to have an article publishing this fall with Pietro Gentile, also from Rome, Italy, documenting the benefits of PRP. We are lucky to have the opportunity to study the combination of PRP and adipose enriched stem cells on hair loss with Dr. Gentile. We are also affiliated with Paul Rose and Bernie Nussbaum in a similar study in Miami.

However, the capacity to study adipose enriched stem cells is far greater in Italy than in the USA (Dr. Joseph Greco’s work and collaborations seem to also support this theory when it comes to PRP). With this in mind, Dr. Insalaco and I are forming an office in collaboration in Rome, Italy with the intent to further study the benefits of regenerative medicine on hair loss. Dr. Insalaco spent the past year training with me in my offices in Los Angeles and Atlanta. She plans to open both a hospital and private practice research center focused on the treatment of hair loss in Rome, Italy. I will be assisting her in this enterprise because she is a gifted surgeon and meticulous researcher. I look forward to continued collaboration with her.

I was thrilled to speak at the 7th conference on regenerative medicine in Rome last December and look forward to speaking at the 8th conference on regenerative medicine in Rome next December. The future of PRP seems to be a combination with adipose enriched stem cells, and there is not a better place to study this than in Italy at the moment (There are also many ongoing studies on ADSC in the US).

So here is the study as follows:

The current study model is to apply Angel Arthrex PRP at a 2 or 3% hematocrit on one side and to activate this with Calcium Gluconate on one-half of the scalp. We have found that calcium gluconate activation offers no statistical difference from PRP activated by bovine thrombin, and it is quite safe. Bovine thrombin carries the risk of a hypersensitivity reaction or antibody response to the foreign thrombin. There are no documented cases of plasmid transmission from Bovine thrombin, but this is a concern some have. Plasmids seem to come only from the bovine neural tissue.

Calcium gluconate, on the other hand, is quite safe. On the other side of the scalp, we are applying sonicated PRP. We know that sonicated PRP helps promote far faster hair growth from transplants than standard PRP. However, we are no sure if sonicated PRP will produce a better response in areas of hair loss. An evaluation of density and hair mass are the purpose of the study.

Sonicated PRP is PRP prepared by exposing your own PRP to a higher energy sound wave intended to lyse the platelets and release a much higher concentration of growth factors than can be obtained through activation with calcium gluconate. Some growth factors are increased by 5 to 8 times the concentration of growth factors activated by calcium gluconate. Sonicated PRP is also very safe.

Sonicated PRP requires the use of an expensive machine designed to deliver a known energy for a variable duration of time. We have found that sonication for 30 seconds on and 30 seconds off for a total of one hour produces the highest concentration of growth factors.

The typical cost for PRP is $5000.00 for three treatments. In the study, you will receive three treatments for $750.00 each.

In this study, we will not perform a trichoscan. A trichoscan requires us to trim to 1mm approximately 2 cm2 surface area of hair. Trimming just over 2 square cm can be difficult for individuals to conceal. Therefore, we will be looking at density, diameter, and the hair check because this requires a much small surface area of hair trimming and should not be noticeable. While we did see a positive response on the trichoscan in our previous study, we are eliminating this from the present study. The hair check will require your hair be at least 2 inches long for present and future follow-ups.

In the study, we will want to see you at 3, 6, and 12 months following treatments. We recommend the following treatment protocol. However, we would accept a single treatment provided you make your follow up appointments. We recommend the first treatment at day one, the second treatment at day 90, the third treatment at day 180. However, a single treatment is also possible.

We also know that almost all women respond to PRP. Furthermore, we have a new exciting product for men and females that is a Wnt up regulator (I am skeptical that an individual doctor can develop this when companies can not/are not, but glad Dr. Cole is trying out new things). The Wnt pathway has been shown to increase hair growth.

In a study performed by Antonella Tosti, she found this product improved the Hair Check in the female population of patients she studied. She did not examine this product in men in her study. A positive response in the hair check is a more significant response than an increase in density because an improvement in hair mass ensures better coverage.

I can send you some specific one-year data on both Regen and Arthrex if you like (I do not plan to ask for this).

Regards,

Dr. Cole