elliotramsey
Established Member
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Y'all have got me completely confused.. So I'm gonna leave this thread to you. Best of luck
Why is the thinning area in male pattern baldness exactly the galea area ?
- Thread starter cyberprimate
- Start date
S Foote.
Experienced Member
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For a long time now when talking about new ideas relating to male pattern baldness on the forums, someone will always quote the old in-vitro studies (test tube). They claim these studies prove beyond question that the action of androgens in male pattern baldness, is a direct one upon the DP cells synergisticly with other follicle cells. So any other ideas are not valid.
I have argued many times my reasons for thinking this conclusion is misleading in respect of what is happening in-vivo (in the body). The posts are on the forums, and i wont go over old ground here. There are however a couple of abstracts of intrest at the bottom of this post, that also demonstrate some of the issues with culturing male pattern baldness DP cells for in-vitro testing.
There is now a fairly recent in-vivo study, that clearly demonstrates that the old claim about the in-vitro studies above is wrong. I think the time is now long overdue to put these old assumptions aside and move on.
This study is known on the forums, and concerns the transplantaion of human miniaturised male pattern baldness follicles into immune deficient mice.
These are "NOT" androgen deficient mice, and there was more than enough androgens present to maintain these male pattern baldness follicles in miniaturisation if the "direct" theory is correct. Yet the transplanted male pattern baldness follicles significantly regrew!
Putting aside any other implications of this very important study, it must be emphasised that at the very least this throws out any validity of the in-vitro studies quoted.
Some may try to claim that the androgen levels were not high enough in the mice to effect the transplanted follicles. But thats not a claim the direct theory makes! It claims follicle sensitivity to, not levels of androgens.
This study obviously also goes against the old donor dominance theory. This and the in-vitro studies were all the old "direct" action of DHT theory had going for it, so definately time to move on!
S Foote.
Study of Cell Senescence in Cultured
Primary Balding and Non-Balding
Dermal Papilla Cells
A.W. Bahta
Dermatology (QMUL), London, UK
The dermal papilla (DP) expresses androgen receptors and is
known to control normal hair growth. The paradox of androgen action
in human hair growth is well established but the molecular mechanisms
are poorly understood. DP cells derived from frontal (balding)
human scalp hair follicles (BDPC) are used to study androgenetic
alopecia. Cultured BDPC are known to have a much slower rate of
growth in vitro than DP from non-balding sites (NBDPC), however,
the cause of this has not been reported.
In this study we have investigated
the growth of human BDPC and NBDPC in vitro. We observed
that BDPC have a limited life span of 2–6 passages. We observed that
from passage 2 onwards BDPC but not NBDPC showed a large flattened
morphology characteristic of senescent fibroblasts and that
once they had assumed this morphology they could no longer be
passaged. We showed that these BDPC but not NBDPC of the same
passage expressed senescence-associated -galactosidase activity at
pH-6. Moreover, stress-induced premature senescence was induced
with more prominent characteristic behaviour in BDPC than NBDPC
after exposure to sub-cytotoxic levels of H2O2 a known inducer of
oxidative stress. Finally BDPC also expressed a wide range of oxidative
stress markers including HSP27, Super Oxide Dismutase and
Catalase. These data suggest that the well documented, slower in vitro
proliferative rate of BDPC is due in part to premature senescence.
Moreover, our observation that cultured BDPC express markers of
oxidative stress and their response to H2O2 suggest that oxidative
stress may play a major role in male pattern hair loss. Others and we
have observed that DHT is able to induce TGF-1 in BDPC. TGF-1
is known to induce oxidative stress and this may therefore, link androgens
with oxidative stress and help explain the paradox of androgen
action on hair growth.
-------------------------------
P4
Initial Characterisation of a New Model of
Dermal Papilla Cell Culture
C. Higgins1, G. Richardson1, G. Westgate2, M. Green3,
D.J. Tobin4, C. Jahoda1
1Department of Biological Sciences, Durham University,
2Westgate Consultancy, Stevington, Bedfordshire, 3Unilever
R&D Colworth, Sharnbrook, Bedford, 4School of Life
Sciences, University of Bradford, UK
Human dermal papilla (DP) cells grown in culture have been studied
extensively. However, some key differences between DP cell
behaviour in vivo and in culture have been identified. Smooth muscle
actin (SMA) is a sheath-cell specific marker in vivo, but once in
culture both papilla and sheath cells express SMA. Cells derived
from anagen DP’s are highly proliferative whilst the same cells in vivo
do not proliferate. Expression of extracellular matrix proteoglycans
changes during the hair cycle. The chondroitin proteoglycan Bamacan
is expressed in the anagen DP yet lost on entry to catagen and telogen
whilst Syndecan-1 is absent in anagen but present in the telogen DP.
In contrast, Perlecan expression remains constant throughout the hair
cycle. We previously demonstrated that DP cells grown in suspension
culture in tiny volumes form small spheroids which appear morphologically
to be more akin to DP found in vivo. We have now investigated
the differences between the two culture conditions using the
expression profile of SMA, proteoglycans and markers of proliferation.
Human DP cells at P4/P5 were plated in 35 mm dishes or placed
in hanging drops. All cells were cultured in MEM containing 10%
FBS. Cells were harvested when 80–90% confluent whilst spheres
were harvested after 30 h in culture. The two culture methods were
compared using RT-PCR and immuno-cytochemistry. The integrity
and viability of the spheres was confirmed using TEM and viability
markers. Results show that dermal spheres have a different profile
from normally cultured DP cells suggesting spheres may be an interesting
new model for studying DP cells in vitro. Perlecan and
Syndecan-1 expression is similar in both cells and dermal spheres in
contrast to Bamacan which is reduced in dermal spheres. SMA and
Ki67 are expressed in DP cells but not in dermal spheres, even though
the spheres remained viable.
I have argued many times my reasons for thinking this conclusion is misleading in respect of what is happening in-vivo (in the body). The posts are on the forums, and i wont go over old ground here. There are however a couple of abstracts of intrest at the bottom of this post, that also demonstrate some of the issues with culturing male pattern baldness DP cells for in-vitro testing.
There is now a fairly recent in-vivo study, that clearly demonstrates that the old claim about the in-vitro studies above is wrong. I think the time is now long overdue to put these old assumptions aside and move on.
This study is known on the forums, and concerns the transplantaion of human miniaturised male pattern baldness follicles into immune deficient mice.
These are "NOT" androgen deficient mice, and there was more than enough androgens present to maintain these male pattern baldness follicles in miniaturisation if the "direct" theory is correct. Yet the transplanted male pattern baldness follicles significantly regrew!
Putting aside any other implications of this very important study, it must be emphasised that at the very least this throws out any validity of the in-vitro studies quoted.
Some may try to claim that the androgen levels were not high enough in the mice to effect the transplanted follicles. But thats not a claim the direct theory makes! It claims follicle sensitivity to, not levels of androgens.
This study obviously also goes against the old donor dominance theory. This and the in-vitro studies were all the old "direct" action of DHT theory had going for it, so definately time to move on!
S Foote.
Study of Cell Senescence in Cultured
Primary Balding and Non-Balding
Dermal Papilla Cells
A.W. Bahta
Dermatology (QMUL), London, UK
The dermal papilla (DP) expresses androgen receptors and is
known to control normal hair growth. The paradox of androgen action
in human hair growth is well established but the molecular mechanisms
are poorly understood. DP cells derived from frontal (balding)
human scalp hair follicles (BDPC) are used to study androgenetic
alopecia. Cultured BDPC are known to have a much slower rate of
growth in vitro than DP from non-balding sites (NBDPC), however,
the cause of this has not been reported.
In this study we have investigated
the growth of human BDPC and NBDPC in vitro. We observed
that BDPC have a limited life span of 2–6 passages. We observed that
from passage 2 onwards BDPC but not NBDPC showed a large flattened
morphology characteristic of senescent fibroblasts and that
once they had assumed this morphology they could no longer be
passaged. We showed that these BDPC but not NBDPC of the same
passage expressed senescence-associated -galactosidase activity at
pH-6. Moreover, stress-induced premature senescence was induced
with more prominent characteristic behaviour in BDPC than NBDPC
after exposure to sub-cytotoxic levels of H2O2 a known inducer of
oxidative stress. Finally BDPC also expressed a wide range of oxidative
stress markers including HSP27, Super Oxide Dismutase and
Catalase. These data suggest that the well documented, slower in vitro
proliferative rate of BDPC is due in part to premature senescence.
Moreover, our observation that cultured BDPC express markers of
oxidative stress and their response to H2O2 suggest that oxidative
stress may play a major role in male pattern hair loss. Others and we
have observed that DHT is able to induce TGF-1 in BDPC. TGF-1
is known to induce oxidative stress and this may therefore, link androgens
with oxidative stress and help explain the paradox of androgen
action on hair growth.
-------------------------------
P4
Initial Characterisation of a New Model of
Dermal Papilla Cell Culture
C. Higgins1, G. Richardson1, G. Westgate2, M. Green3,
D.J. Tobin4, C. Jahoda1
1Department of Biological Sciences, Durham University,
2Westgate Consultancy, Stevington, Bedfordshire, 3Unilever
R&D Colworth, Sharnbrook, Bedford, 4School of Life
Sciences, University of Bradford, UK
Human dermal papilla (DP) cells grown in culture have been studied
extensively. However, some key differences between DP cell
behaviour in vivo and in culture have been identified. Smooth muscle
actin (SMA) is a sheath-cell specific marker in vivo, but once in
culture both papilla and sheath cells express SMA. Cells derived
from anagen DP’s are highly proliferative whilst the same cells in vivo
do not proliferate. Expression of extracellular matrix proteoglycans
changes during the hair cycle. The chondroitin proteoglycan Bamacan
is expressed in the anagen DP yet lost on entry to catagen and telogen
whilst Syndecan-1 is absent in anagen but present in the telogen DP.
In contrast, Perlecan expression remains constant throughout the hair
cycle. We previously demonstrated that DP cells grown in suspension
culture in tiny volumes form small spheroids which appear morphologically
to be more akin to DP found in vivo. We have now investigated
the differences between the two culture conditions using the
expression profile of SMA, proteoglycans and markers of proliferation.
Human DP cells at P4/P5 were plated in 35 mm dishes or placed
in hanging drops. All cells were cultured in MEM containing 10%
FBS. Cells were harvested when 80–90% confluent whilst spheres
were harvested after 30 h in culture. The two culture methods were
compared using RT-PCR and immuno-cytochemistry. The integrity
and viability of the spheres was confirmed using TEM and viability
markers. Results show that dermal spheres have a different profile
from normally cultured DP cells suggesting spheres may be an interesting
new model for studying DP cells in vitro. Perlecan and
Syndecan-1 expression is similar in both cells and dermal spheres in
contrast to Bamacan which is reduced in dermal spheres. SMA and
Ki67 are expressed in DP cells but not in dermal spheres, even though
the spheres remained viable.
elliotramsey
Established Member
- Reaction score
- 14
I curious to know exactly what it means in laymen's as well. Although i have been looking for something to disprove the "in vitro" argument for quite some time.
Thanks S Foote.!
Thanks S Foote.!
S Foote.
Experienced Member
- Reaction score
- 66
I think we have to be carefull about pointing the finger at oxidative stress in itself as the "cause" of male pattern baldness. Purely because this still fails to explain the transplantation growth.
I think it is certainly more support for the existence of a "stagnant" circulation in the male pattern baldness scalp. Someone posted a study in this thread about lack of oxygen in the male pattern baldness scalp, and i think there are others.
S Foote.
I think it is certainly more support for the existence of a "stagnant" circulation in the male pattern baldness scalp. Someone posted a study in this thread about lack of oxygen in the male pattern baldness scalp, and i think there are others.
S Foote.
S Foote.
Experienced Member
- Reaction score
- 66
idontwanttobebalding said:
I dont think it is the same players necessarily in all the conditions you reference. We have to try to keep it as simple as possible.
In this respect, in my theory both the oxidative stress and the Wnts pathway in male pattern baldness, are simply linked by scalp edema. This accounts for the hypoxia in the tissue, and the pressure acts on the follicles to produce early contact inhibition of follicle growth. Wnts and ß-Catenin are known to be involved in the contact inhibition proccess.
Fuchs did a study in mice where playing around with Wnts produced much increased hair growth, and also tumors. This indicates a loss of the "normal" contact inhibition of cell growth. We "DO NOT" want to be messing around with Wnts etc!
There may be many interactions that dictate an individuals susceptibility to the other conditions you mention. One important implication of my theory that DHT increases lymphatic drainage, is that this would protect men from many autoimmune conditions suffered by women. On the whole, women suffer far more than men from autoimmune conditions. There is good reason to think that DHT increases immune traffic so protecting men.
Remember, i contend that the conditions in the male pattern baldness scalp are "opposite" because of the plumbing layout. So we get immune infiltrate and stagnation in male pattern baldness, leading to the question often raised of male pattern baldness being an autoimmune issue. But according to my theory, this is just one of the side effects of the edema, as is the fibrosis that developes.
These are all known to be linked to edema. Here is an article about the effects of lymphedema, which is what i think we are dealing with in male pattern baldness. this demonstrates how lasers can help.
http://www.lymphedemapeople.com/thesite ... atment.htm
Quote:
"Lymphoedema is a progressive condition with four main characteristics (1):
1. excessive protein in the tissues
2. excessive fluid in the tissues (both intra and extracellular fluid)
3. excessive deposition of fibrous tissue
4. chronic inflammatory reactions.
The excess fluid and fibre are immediately under the skin and well within the reach of the laser beam. New lymph vessels cannot grow through scar tissue or fibrosed tissues. Following laser therapy there is a softening of the tissues and reduction in the fluid. New lymph vessels can grow (2). The limbs do not reduce in size until there is softening."
S Foote.
S Foote.
Experienced Member
- Reaction score
- 66
idontwanttobebalding
I think that last link is interesting, certainly massage is good.
What i see as the ultimate one off solution if you like, is a surgical procedure that modifies the "plumbing" to reduce the feed and increase the drainage in the scalp. Then we become like those men who do not develope male pattern baldness according to my theory. Such a developed procedure would certainly not be as drastic as transplantation. I think this is what removing the galea helps with. Bryan has a link to a study involving reducing the feed side through blood vessel ligiture.
For now, i think we have to treat the area as you would treat lymphedema. Massage is used here, and lasers prove effective, but it has to be the right kind of laser, and not overdone. I use the original "cheap" laser brush people will be familiar with, for 5 to 10 mins brushing from the crown outwards. I think it is counter productive to do more, and i have had noticable results.
We must not overdo things or be too harsh, as to cause any more inflammation. I do not agree with the scalp wounding idea at all for this reason.
You will be aware of Toms scalp exercises, and again i think this moves fluid which is the important thing. There are many discussions on these forums about things that help, and i think the common factor is moving fluid away from the follicles. There are currently studies using the latinoprost type substances in male pattern baldness, that were developed to reduce fluid pressure in the eye.
I also think that if you have time alone around 15/20 mins a day, an ice pack on the scalp can make a noticable difference to scalp irritation, and hair growth and quality. Again this is a normal thing to do when dealing with "swelling", which is the bottom line in my theory.
I think modern humans are still capable of growing more hair in response to cold, as demonstrated by the ice carriers who hauled sacks of ice on their backs before refrigeration. They grew thick hair on their backs.
So in my opinion. regular gentle massage, laser treatment, scalp cooling, washing hair with cool water, and avoiding scalp sunburn or chemical abuse is all good. Anything that avoids more inflammation and moves fluid is good.
S Foote.
I think that last link is interesting, certainly massage is good.
What i see as the ultimate one off solution if you like, is a surgical procedure that modifies the "plumbing" to reduce the feed and increase the drainage in the scalp. Then we become like those men who do not develope male pattern baldness according to my theory. Such a developed procedure would certainly not be as drastic as transplantation. I think this is what removing the galea helps with. Bryan has a link to a study involving reducing the feed side through blood vessel ligiture.
For now, i think we have to treat the area as you would treat lymphedema. Massage is used here, and lasers prove effective, but it has to be the right kind of laser, and not overdone. I use the original "cheap" laser brush people will be familiar with, for 5 to 10 mins brushing from the crown outwards. I think it is counter productive to do more, and i have had noticable results.
We must not overdo things or be too harsh, as to cause any more inflammation. I do not agree with the scalp wounding idea at all for this reason.
You will be aware of Toms scalp exercises, and again i think this moves fluid which is the important thing. There are many discussions on these forums about things that help, and i think the common factor is moving fluid away from the follicles. There are currently studies using the latinoprost type substances in male pattern baldness, that were developed to reduce fluid pressure in the eye.
I also think that if you have time alone around 15/20 mins a day, an ice pack on the scalp can make a noticable difference to scalp irritation, and hair growth and quality. Again this is a normal thing to do when dealing with "swelling", which is the bottom line in my theory.
I think modern humans are still capable of growing more hair in response to cold, as demonstrated by the ice carriers who hauled sacks of ice on their backs before refrigeration. They grew thick hair on their backs.
So in my opinion. regular gentle massage, laser treatment, scalp cooling, washing hair with cool water, and avoiding scalp sunburn or chemical abuse is all good. Anything that avoids more inflammation and moves fluid is good.
S Foote.
cyberprimate
Established Member
- Reaction score
- 14
Interesting study: the injection of botox to the muscles tightening the galea altered hair loss of subjects with male pattern baldness.
http://journals.lww.com/plasreconsurg/F ... um.79.aspx
http://journals.lww.com/plasreconsurg/F ... um.79.aspx
Attachments
S Foote.
Experienced Member
- Reaction score
- 66
idontwanttobebalding said:
Thanks for the link, i did read the paper about this. I note other "pressure" theories are being proposed, like the skull growth idea.
In my opinion however, they fail to address the issue in a proper scientific manner. We should remember the question we want answered? People tend to just focus on the male pattern baldness issue, but in true scientific terms the question is "how do androgens effect hair growth"? This includes androgen related increases in hair growth.
These theories don't explain this without adding another mechanism. We also have the issue of how do transplants get around this pressure? Something else to consider. If the claim is that the pressure is reducing the blood supply and causing hair loss through "starvation" and hypoxia, there is a major flaw in it.
We know through common observation that terminal hair growth continues in some follicles in bald areas. These can keep growing for years, before the area becomes slick bald. This wouldn't happen if the mechanism was as described above.
In my theory, all that is needed is for androgens, in particular DHT to increase the lymphatic pumping rate. This accounts for the hair growth and male pattern baldness in some by known physiology, and fluid dynamic principles. The survival of transplants how i proposed earlier, and the survival of some follicles for long periods because contact inhibition only happens to new enlarging anagen follicles.
Any valid theory must address these issues.
S Foote.