Revisiting Important Findings - Implications for De novo Hair Growth

The following is the mechanism required to stimulate a variety of factors to stimulate new hair growth. Most notably Platelet-derived growth factor (PDGF) and VEGF.

That mechanism is short-term hypoxia (without oxygen), which stimulates a production of factors which will help further the factors (cytokines) necessary to facilitate better oxygen transport to the dermal papilla.

Take a look at the information below to get an idea of the why. The question I have is, what would be the most effective way to induce short-term hypoxia to the scalp?

Biomed Res. 2010 Feb;31(1):27-34.
Hair growth stimulated by conditioned medium of adipose-derived stem cells is enhanced by hypoxia: evidence of increased growth factor secretion.
Park BS, Kim WS, Choi JS, Kim HK, Won JH, Ohkubo F, Fukuoka H.

Leaders Clinic, Seoul, Korea.

Adipose-derived stem cells (ADSCs) and their secretomes mediate diverse skin-regeneration effects, such as wound-healing and antioxidant protection, that are enhanced by hypoxia. We investigated the hair-growth-promoting effect of conditioned medium (CM) of ADSCs to determine if ADSCs and their secretomes regenerate hair and if hypoxia enhances hair regeneration. If so, we wanted to identify the factors responsible for hypoxia-enhanced hair-regeneration. We found that ADSC-CM administrated subcutaneously induced the anagen phase and increased hair regeneration in C(3)H/NeH mice. In addition, ADSC-CM increased the proliferation of human follicle dermal papilla cells (HFDPCs) and human epithelial keratinocytes (HEKs), which are derived from two major cell types present in hair follicles. We investigated the effect of hypoxia on ADSC function using the same animal model in which hypoxia increased hair regrowth. Forty-one growth factors in ADSC-CM from cells cultured under hypoxic or normoxic conditions were analyzed. The secretion of insulin-like growth factor binding protein (IGFBP)-1, IGFBP-2, macrophage colony-stimulating factor (M-CSF), M-CSF receptor, platelet-derived growth factor receptor-beta, and vascular endothelial growth factor was significantly increased by hypoxia, while the secretion of epithelial growth factor production was decreased. It is reasonable to conclude that ADSCs promote hair growth via a paracrine mechanism that is enhanced by hypoxia.


Full Study: http://www.jstage.jst.go.jp/article/biomedres/31/1/27/_pdf

J Dermatol Sci. 2006 Aug;43(2):105-15. Epub 2006 May 24.
PDGF isoforms induce and maintain anagen phase of murine hair follicles.
Tomita Y, Akiyama M, Shimizu H.

Department of Dermatology, Hokkaido University Graduate School of Medicine, N15 W7 Sapporo 060-8638, Japan.

BACKGROUND:
It is known that platelet-derived growth factor (PDGF) receptors are expressed in hair follicle (HF) epithelium.
OBJECTIVES:
The aim of the present study was to clarify the effects of PDGF-AA and -BB on the cyclic growth of HFs.
METHODS:
PDGF-AA or -BB was injected into the dorsal skin of C3H mice during the second telogen phase once daily for five consecutive days, or PDGF-AA or -BB dissolved in hyaluronic acid was injected only once. In order to confirm the effects of different PDGF isoforms, anti-PDGF-AA antibody or anti-PDGF-BB antibody was injected just after each injection of PDGF-AA or -BB. In addition, anti-PDGF antibodies were injected into the skin of C3H mice during the second anagen phase once daily for 5 days. We studied expression of signaling molecules in the skin where anagen phase had been induced by PDGF injection by real-time RT-PCR.
RESULTS:
Both PDGF-AA and -BB injection experiments immediately induced the anagen phase of the hair growth cycle at the injection sites. The induction of anagen was interfered by anti-PDGF antibody treatment. Real-time RT-PCR using extracted RNA from the PDGF injected sites of skin samples showed upregulated expression of HF differentiation-related key signaling molecules, Sonic hedgehog (Shh), Lef-1 and Wnt5a.
CONCLUSIONS:
These results indicate that both PDGF-AA and -BB are involved in the induction and maintenance of the anagen phase in the mouse hair cycle. Local application of PDGF-AA and -BB might therefore prove to be an effective treatment option for alopecia associated with early catagen induction and elongated telogen phase.

I'm not sure how the follicles are fed with oxygen, does the blood travel between the skin and the skull? If so it seems like some surgical tubing could be used to cut off the blood supply using a quick release knot like they make when drawing blood.

How would you tell if the blood's been adequately cut off?

sdguy wrote:I'm not sure how the follicles are fed with oxygen, does the blood travel between the skin and the skull? If so it seems like some surgical tubing could be used to cut off the blood supply using a quick release knot like they make when drawing blood.

How would you tell if the blood's been adequately cut off?

so cutting off blood supply will stimulate hair growth? This flies contrary to some other opinions, like the Malinak method, which says not enough blood is flowing to the scalp due to stress.

Will be interested to hear what comes of this path, but I would be a little bit skeptical for site injections on my head!

zanza wrote:

sdguy wrote:I'm not sure how the follicles are fed with oxygen, does the blood travel between the skin and the skull? If so it seems like some surgical tubing could be used to cut off the blood supply using a quick release knot like they make when drawing blood.

How would you tell if the blood's been adequately cut off?

so cutting off blood supply will stimulate hair growth? This flies contrary to some other opinions, like the Malinak method, which says not enough blood is flowing to the scalp due to stress.

Will be interested to hear what comes of this path, but I would be a little bit skeptical for site injections on my head!

It's only short term, which causes the body to stimulate pathways to increase oxygen.

Maybe very large amounts of alcohol or caffeine.

CausticSymmetry wrote:

zanza wrote:

sdguy wrote:I'm not sure how the follicles are fed with oxygen, does the blood travel between the skin and the skull? If so it seems like some surgical tubing could be used to cut off the blood supply using a quick release knot like they make when drawing blood.

How would you tell if the blood's been adequately cut off?

so cutting off blood supply will stimulate hair growth? This flies contrary to some other opinions, like the Malinak method, which says not enough blood is flowing to the scalp due to stress.

Will be interested to hear what comes of this path, but I would be a little bit skeptical for site injections on my head!

It's only short term, which causes the body to stimulate pathways to increase oxygen.

What duration are we talking, seconds, minutes, hours?

Paraphrasing from the study "When adipose derived stem cells (ADSCs) are cultured under hypoxic conditions (in vitro), their proliferative and self renewal capacities are significantly improved. Hypoxia amplifies the paracrine effects of the ADSCs--increasing growth factors."

How long was the low oxygen? Quite long in this case and it was in vitro--2% oxygen for 72 hours.

There are two challenges being faced here.

The first is extending a decaying network of capillaries. Regardless of the cause of hairloss, as hairs are lost, there is less demand for blood flow, and the network infrastructure supporting the papilla capillary loops diminishes. Essentially, because there is no need.

We cannot easily get this to regenerate.

2nd Challenge - turning hair from vellus to terminal. The main difference here is the absence / presence of a direct capillary loop. At the point hair becomes terminal, it develops a capillary loop to provide the blood it needs. It's been noted that whilst Minxodil only increases blood flow over 2% solutions, it does also increase capillary fenestrations.

I would suggest these fenestrations allows some hairs to cross a threshold that kickstarts regrowth. My unproven premise is that just as hairs going terminal increase local development and a capillary loop - forcing a capillary loop to develop will also cause hair to go terminal. From my own point of view, I feel this is practically demonstrated (to myself).

This kind of growth deals with diffuse thinning - and is poor at extending the network losses due to recession.

Recession requires aniogenesis - and as CS's article points out - hypoxia achieves this.

Ironically hyxpoxia can be achieved in the following ways as well:

Hyperbaric chamber - increased oxygenation triggers a hypoxia like response (reason? perhaps ratio to carbon dioxide)
Pressure - we've all heard about people carrying heavy weights on their shoulders developing hair pads - I believe this also explains the minor success reported with so called 'skull growth' methods

I think the paper CS references holds out the promise of much improved methods in the future.

rdkml wrote:Maybe very large amounts of alcohol or caffeine.

Large amounts of alcohol can burst capillaries.

Have been doing something different recently and also have been thinking about this pressure thing, increasing/stopping blood flow, etc.

In theory, you could take a belt or cord or rubber tubing, tie around the head from the back of the neck and fasten on top near the forehead. Take a shower but alternate hot/cold water on the head for a few minutes. I guess if you wanted to stop blood flow you could just apply the tubing and let the pressure do the rest.

I did the hot/cold scalp deal and noticed a boost from it. Maybe it's forcing the blood pressure around up there.

Sleep Apnea decrease blood flow to the extremities, such as hands, feet and reproductive organs, to the skin and scalp, as your body attempts to keep more blood with the reduced oxygen saturation to important organ functions. The chronic physiologic stress of the OSA screws with your cortisol increasing your cortisol levels. Probably why some OSA sufferers have some form of regrowth once they resolve their OSA as their cortisol levels go back to normal and more blood flow to their extremities.

AbstractSleep and its disorders are increasingly becoming important in our sleep deprived society. Sleep is intricately connected to various hormonal and metabolic processes in the body and is important in maintaining metabolic homeostasis. Research shows that sleep deprivation and sleep disorders may have profound metabolic and cardiovascular implications. Sleep deprivation, sleep disordered breathing, and circadian misalignment are believed to cause metabolic dysregulation through myriad pathways involving sympathetic overstimulation, hormonal imbalance, and subclinical inflammation. This paper reviews sleep and metabolism, and how sleep deprivation and sleep disorders may be altering human metabolism.

Sleep and Metabolism: An Overview

gbp2000 wrote:

rdkml wrote:Maybe very large amounts of alcohol or caffeine.

Large amounts of alcohol can burst capillaries.

I'm not sure what you mean. I might be pretty dense right now but are you getting at that very large quantities won't lower the circulation enough?

Whip wrote:In theory, you could take a belt or cord or rubber tubing, tie around the head from the back of the neck and fasten on top near the forehead.

Sounds like you remember the days when Lava212 popularized that on regrowth.com with some other such as thelibrarian, cuebreeze and others that tried it. Brings back memories, lol.

Here is one link using occlusion training on the scalp for those that aren't aware.

http://www.regrowth.com/hairloss-forums/viewthread.cfm?f=1&t=23900

I had forgotten about all that actually, but lord knows we've tried everything else already. Next week it'll probably be urine and corn starch mixed with vodka

The hot/cold thing has improved texture though, maybe it does something.

It seems certain breathing exercises that produce hyperventilation can produce temporary hypoxia.

fwiw.

http://www.koljavoelkers.de/literatur/articles/Vogiatzis%20et%20al%20%281996%29%20Changes%20in%20ventilation%20related%20to%20changes%20in%20electromyograph%20activity.pdf

Lustucru, to what observation of the paper are you drawing our attention? It's quite a technical one, and requires significant time to read properly with background material, but what in effect are you suggesting in context of hair?

Regarding CO2 all I see is that the authors note how its presence changes with exercise and rest patterns; as also breathing.
"T h e inc r e a s e in P[et]CO2 seen d u r i n g t h e intervals
be twe en bout s , a n d during, e a r ly recovery, always j u s t
preceded a n increase in Vi. I t ha s been s h own t h a t
t r a n s i e n t v e n o u s CO2 l o a d i n g is reflected in an inc r e a s e
in a lveol a r a n d arterial P[et]CO2"

http://bit.ly/zEXFpa (same link, but shortened... previous one was too long and didn't wrap)

just guessing that isometric endurance exercise may give the benefits of hypoxia, while exercising... i am not good enough to decipher this paper though...