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Scalps immune response - study extract


#1

As you know Ive been talking about the immune response for a few years and how its is one of the major factors involved in hairloss. If you can reverse this factor topically and some of the other factors that it triggers -I think youll be well on your way to regrowing hair!

Ive come across this extract in one of the other forums which Bryan has kindly posted ( I tried to copy the link but it wouldnt post so Ive had to copy and paste!) :

"The study below has been cited a few times by various people on hairloss sites over the last couple of years, but I’ve read the whole thing, and I want to present some of the interesting details from it. First of all, here’s the abstract:

J Am Acad Dermatol. 2003 May;48(5):752-9.

“Transplants from balding and hairy androgenetic alopecia scalp regrow hair comparably well on immunodeficient mice”

Krajcik RA, Vogelman JH, Malloy VL, Orentreich N.

“Human hair follicles were grafted onto 2 strains of immunodeficient mice to compare the regeneration potential of vellus (miniaturized, balding) and terminal (hairy, nonbalding) follicles from males and a female exhibiting pattern baldness. Each mouse had transplants of both types of follicles from a single donor for direct comparison. Grafted follicles from 2 male donors resulted in nonsignificant differences in mean length (52 mm vs 54 mm) and mean diameter (99 microm vs 93 microm) at 22 weeks for hairs originating from balding and hairy scalp, respectively, corresponding to 400% versus 62% of the mean pretransplantation diameters. Follicles from the female donor transplanted to several mice also resulted in nonsignificant differences in length (43 mm vs 37 mm) for hairs from balding and hairy scalp, respectively, during a period of 22 weeks. The mean diameter of the originally vellus hairs increased 3-fold, whereas the terminal hairs plateaued at approximately 50% of pretransplantation diameter, resulting in a final balding hair volume double that of the nonbalding hairs. This report shows that miniaturized hair follicles of pattern alopecia can quickly regenerate once removed from the human scalp and can grow as well as or better than terminal follicles from the same individual.”

The abstract gives the salient points: they found that fine vellus hairs from balding human scalps had an EXCEPTIONAL ability to regenerate, when transplanted onto test mice that had severe immune deficiency (they use those for transplant experiments so that the mice don’t suffer rejection of the foreign tissue). In fact, after about 5 to 6 months, transplanted follicles with vellus hairs regrew to the same size as the transplanted terminal hairs in one set of mice, and actually grew LARGER than the terminal hairs in another set of mice (for which phenomenon they don’t yet have any explanation)! Here’s an extended excerpt from the Discussion section at the end in which they speculate about the various implications of their findings:

“…The phenomenon occurring in the xenograft experiments reported here is quite different and dramatic: hypotrophic anagen and telogen hairs from balding scalp exhibiting only vellus hairs in situ regenerate very quickly. By six months, the ratio of the diameters of grafted to pretransplant vellus hairs exceeds 3:1 (Fig 3). Histologic examination of post-transplantation follicles from balding scalp also shows fully developed anagen follicles at six months (Fig 2). The regeneration of vellus follicles occurs just as quickly on male as on female mice (data not shown); this suggests that a factor or factors other than androgen withdrawal may be involved but does not necessarily rule out that differences in androgen levels, availablity, or both between human beings and mice account in part or entirely for the rapid vellus-to-terminal transformation of balding follicles. For instance, the activity of the 5a-R enzyme(s) may be greatly reduced or absent in the transplanted follicles, thereby, limiting exposure of the follicles to DHT. The accelerated transformation of vellus follicles on immunodeficient mice might correspond to responses seen in balding men treated with oral finasteride who are exceptionally good responders. However, in our clinical experience, females with AGA, including the female in study II, frequently have normal androgen and androgen-binding globulin levels for their age and sex. It is difficult to argue that lower systemic androgen levels in the female mouse environment (or higher in the male mice) causes the rapid regeneration of vellus hair follicles from the human female. Therefore, the existence of an inhibitor factor other than androgens, particularly in women showing diffuse/pattern alopecia, that is lacking in the nude mouse seems plausible. This could be some other steroid, hormone, cytokine, neuropeptide, or an immunologically related factor.”

I think that last part about the “immunologically related factor” is an understatement! After reading this paper, it now seems likely that the immune system is an even bigger factor in MPB than was previously thought. I personally had always assumed that the putative attack on hair follicles by the immune system was something that happens relatively late in the game, but this study is awfully compelling. But oddly enough, you see very little about this aspect of balding in the medical literature. Dr. Proctor, OTOH, has talked about it for years on alt.baldspot.

So what really is the point of bringing this up in the first place, this issue “Of Mice and Men”?? Well, I think it can be a source of great hope for all of us! It proves that there exists the POTENTIAL for our poor follicles to regenerate completely all on their own, if only we can figure out how to let that happen. It appears that we may not have to wait for far-off and possibly risky genetic treatments, or puzzle-out all those very complex mesenchymal-epithelial interactions (HM, in other words), or depend on other high-tech treatments. We may find simpler, safer ways to do it, with the additional clues provided by this fascinating study.

Bryan "

Regards
Pete


#2

I read that too and I usually dismiss any experiments that are done in mice. Having been on these boards for so long, I came to realize that mice generally respond far better than humans.

However, I do agree that hair loss is an immune related condition, now the question is what part of our immune system should we target and how?


#3

» I read that too and I usually dismiss any experiments that are done in
» mice. Having been on these boards for so long, I came to realize that mice
» generally respond far better than humans.
»
» However, I do agree that hair loss is an immune related condition, now the
» question is what part of our immune system should we target and how?

You target the scalp via increasing SOD levels, boosting bloodflow and reducing inflammation!

Regards
Pete


#4

» You target the scalp via increasing SOD levels, boosting bloodflow and
» reducing inflammation!

I am not sure how you link these to immune system. To me, immune system is a lot more complicated than blood flows and inflammation. Besides,there are already a lot of products on the market that claim to increase bloodflow for the scalp and reduce inflammation, most of them are only marginally effective.


#5

» » You target the scalp via increasing SOD levels, boosting bloodflow and
» » reducing inflammation!
»
» I am not sure how you link these to immune system. To me, immune system is
» a lot more complicated than blood flows and inflammation. Besides,there are
» already a lot of products on the market that claim to increase bloodflow
» for the scalp and reduce inflammation, most of them are only marginally
» effective.

Yes it is, therefore its best to look at lifestyle factors too:

1)reduce saturated fats
2)reduce sugars
3)reduce duretics
4)reduce stress
5)improve lifestyle

Regards
Pete


#6

» » » You target the scalp via increasing SOD levels, boosting bloodflow and
» » » reducing inflammation!
» »
» » I am not sure how you link these to immune system. To me, immune system
» is
» » a lot more complicated than blood flows and inflammation. Besides,there
» are
» » already a lot of products on the market that claim to increase
» bloodflow
» » for the scalp and reduce inflammation, most of them are only marginally
» » effective.
»
» Yes it is, therefore its best to look at lifestyle factors too:
»
» 1)reduce saturated fats
» 2)reduce sugars
» 3)reduce duretics
» 4)reduce stress
» 5)improve lifestyle
»
»
»
»
»
»
» Regards
» Pete

There is more to it than just lifestyle changes, immunodeficiency related illness are acquired (“secondary”) but some people are born with defects in the immune system or so called primary immunodeficiency, I believe hair loss is mostly primary immunodeficiency beacuse we basically inherit the defective genes from our parents.


#7

» » » » You target the scalp via increasing SOD levels, boosting bloodflow
» and
» » » » reducing inflammation!
» » »
» » » I am not sure how you link these to immune system. To me, immune
» system
» » is
» » » a lot more complicated than blood flows and inflammation.
» Besides,there
» » are
» » » already a lot of products on the market that claim to increase
» » bloodflow
» » » for the scalp and reduce inflammation, most of them are only
» marginally
» » » effective.
» »
» » Yes it is, therefore its best to look at lifestyle factors too:
» »
» » 1)reduce saturated fats
» » 2)reduce sugars
» » 3)reduce duretics
» » 4)reduce stress
» » 5)improve lifestyle
» »
» »
» »
» »
» »
» »
» » Regards
» » Pete
»
» There is more to it than just lifestyle changes, immunodeficiency related
» illness are acquired (“secondary”) but some people are born with defects in
» the immune system or so called primary immunodeficiency, I believe hair
» loss is mostly primary immunodeficiency beacuse we basically inherit the
» defective genes from our parents.

Hairloss is due to the follicles shrinking in the presence of DHT and then the immune system attacks these follicles.

Regards
Pete


#8

» Hairloss is due to the follicles shrinking in the presence of DHT and then
» the immune system attacks these follicles.
»
»
» Regards
» Pete

Pete, I don’t think the scientists really know WHY we are losing our hair, what you said is just one of the many many possible reasons for hair loss. There are tons of anti DHT products on the market, wouldn’t you think we would have reversed our hair loss by now if it is as simple as that?

btw, I agree with Therapy, hair loss is probably 70% genetic and 30% environmental.


#9

» » Hairloss is due to the follicles shrinking in the presence of DHT and
» then
» » the immune system attacks these follicles.
» »
» »
» » Regards
» » Pete
»
» Pete, I don’t think the scientists really know WHY we are losing our hair,
» what you said is just one of the many many possible reasons for hair loss.
» There are tons of anti DHT products on the market, wouldn’t you think we
» would have reversed our hair loss by now if it is as simple as that?
»
» btw, I agree with Therapy, hair loss is probably 70% genetic and 30%
» environmental.

I think hormonal balance is key to slow hairloss. It can be achieved via reducing DHT and reducing the factors which contribute to the upregulation. This may make it easier to approach the immune response topically.

Regards
Pete


#10

Hormonal monkeying works but not in the way we really need. It’s a crutch and it has too many side effects.

Normal men without genetic MPB don’t have less androgens in their scalps than we do. They can leave their hormone levels alone and their hair grows just fine.


#11

» Hormonal monkeying works but not in the way we really need. It’s a crutch
» and it has too many side effects.
»
»
» Normal men without genetic MPB don’t have less androgens in their scalps
» than we do. They can leave their hormone levels alone and their hair grows
» just fine.

Yep, there needs to be hormonal balance and at best it will slow hairloss.

As I feel that the immune response is so important - I think a clue is to look at immune related scalp conditions ie AA.

Please cite a reference for the statement ie androgen levels in non balding scalps in comparision with MPB scalps.

Regards
Pete


#12

I’m not a reference-citer.

I remember things pretty well on the whole, but I’m not trying to present myself as someone reliable enough to whip out proof any time I say something.

The androgens in the scalp has been tested though. I think there might actually indeed be slightly higher androgens in balding scalps according to some study.

But the relevant point I was making is that we’re not balding because of some huge abormal over-abundance of adrogens. We’re balding because even just normal levels of androgens in our systems are damaging our hair follicles due to genetic susceptibiliy & past cumulative exposure.

I’m saying that trying to drastically reduce androgens in the scalp is no more of a natural condition for us than artificially reducing the inflammation or something. We need a solution for MPB that doesn’t monkey with the androgen levels if we want a side-effects-free situation.


#13

» The androgens in the scalp has been tested though. I think there might
» actually indeed be slightly higher androgens in balding scalps according to
» some study.

Yes id go with that!

» I’m saying that trying to drastically reduce androgens in the scalp is no
» more of a natural condition for us than artificially reducing the
» inflammation or something. We need a solution for MPB that doesn’t monkey
» with the androgen levels if we want a side-effects-free situation.

When you balance your hormones, you shouldnt have any side effects. If you just concentrate on DHT there will be extra conversion to Estradiol via aromatase. So balance is key, rather than reducing 5ar as much as possible.

Hopefully there will be a good bunch of topicals out at some point, which will help with the immune response to balance it and promote hairgrowth.

Regards
Pete


#14

Naturally balanced hormone levels wouldn’t have any side effects . . . except rapidly continuing hair loss.

This is the point I keep getting back to. The “correct” and “healthy” condition for a man with worsening MPB is to be losing his hair. No amount of righting his unhealthy system is gonna stop his continuing hair loss.

Fighting inflammation is certainly worthy of effort, but we still just need topical AAs that are really practical & effective as much as anything else.


#15

» Naturally balanced hormone levels wouldn’t have any side effects . . .
» except rapidly continuing hair loss.

We will have to agree to disagree, you should be able to slow your hairloss by modifying your diet and taking a few herbs.

I havent come across a good topical for MPB yet.

Regards
Pete


#16

» As you know Ive been talking about the immune response for a few years and
» how its is one of the major factors involved in hairloss. If you can
» reverse this factor topically and some of the other factors that it
» triggers -I think youll be well on your way to regrowing hair!
»
»
» Ive come across this extract in one of the other forums which Bryan has
» kindly posted ( I tried to copy the link but it wouldnt post so Ive had to
» copy and paste!) :
»
»
»
»
»
» "The study below has been cited a few times by various people on hairloss
» sites over the last couple of years, but I’ve read the whole thing, and I
» want to present some of the interesting details from it. First of all,
» here’s the abstract:
»
» J Am Acad Dermatol. 2003 May;48(5):752-9.
»
» “Transplants from balding and hairy androgenetic alopecia scalp regrow
» hair comparably well on immunodeficient mice”
»
» Krajcik RA, Vogelman JH, Malloy VL, Orentreich N.
»
» “Human hair follicles were grafted onto 2 strains of immunodeficient mice
» to compare the regeneration potential of vellus (miniaturized, balding) and
» terminal (hairy, nonbalding) follicles from males and a female exhibiting
» pattern baldness. Each mouse had transplants of both types of follicles
» from a single donor for direct comparison. Grafted follicles from 2 male
» donors resulted in nonsignificant differences in mean length (52 mm vs 54
» mm) and mean diameter (99 microm vs 93 microm) at 22 weeks for hairs
» originating from balding and hairy scalp, respectively, corresponding to
» 400% versus 62% of the mean pretransplantation diameters. Follicles from
» the female donor transplanted to several mice also resulted in
» nonsignificant differences in length (43 mm vs 37 mm) for hairs from
» balding and hairy scalp, respectively, during a period of 22 weeks. The
» mean diameter of the originally vellus hairs increased 3-fold, whereas the
» terminal hairs plateaued at approximately 50% of pretransplantation
» diameter, resulting in a final balding hair volume double that of the
» nonbalding hairs. This report shows that miniaturized hair follicles of
» pattern alopecia can quickly regenerate once removed from the human scalp
» and can grow as well as or better than terminal follicles from the same
» individual.”
»
» The abstract gives the salient points: they found that fine vellus hairs
» from balding human scalps had an EXCEPTIONAL ability to regenerate, when
» transplanted onto test mice that had severe immune deficiency (they use
» those for transplant experiments so that the mice don’t suffer rejection of
» the foreign tissue). In fact, after about 5 to 6 months, transplanted
» follicles with vellus hairs regrew to the same size as the transplanted
» terminal hairs in one set of mice, and actually grew LARGER than the
» terminal hairs in another set of mice (for which phenomenon they don’t yet
» have any explanation)! Here’s an extended excerpt from the Discussion
» section at the end in which they speculate about the various implications
» of their findings:
»
» “…The phenomenon occurring in the xenograft experiments reported here is
» quite different and dramatic: hypotrophic anagen and telogen hairs from
» balding scalp exhibiting only vellus hairs in situ regenerate very quickly.
» By six months, the ratio of the diameters of grafted to pretransplant
» vellus hairs exceeds 3:1 (Fig 3). Histologic examination of
» post-transplantation follicles from balding scalp also shows fully
» developed anagen follicles at six months (Fig 2). The regeneration of
» vellus follicles occurs just as quickly on male as on female mice (data not
» shown); this suggests that a factor or factors other than androgen
» withdrawal may be involved but does not necessarily rule out that
» differences in androgen levels, availablity, or both between human beings
» and mice account in part or entirely for the rapid vellus-to-terminal
» transformation of balding follicles. For instance, the activity of the 5a-R
» enzyme(s) may be greatly reduced or absent in the transplanted follicles,
» thereby, limiting exposure of the follicles to DHT. The accelerated
» transformation of vellus follicles on immunodeficient mice might correspond
» to responses seen in balding men treated with oral finasteride who are
» exceptionally good responders. However, in our clinical experience, females
» with AGA, including the female in study II, frequently have normal androgen
» and androgen-binding globulin levels for their age and sex. It is difficult
» to argue that lower systemic androgen levels in the female mouse
» environment (or higher in the male mice) causes the rapid regeneration of
» vellus hair follicles from the human female. Therefore, the existence of an
» inhibitor factor other than androgens, particularly in women showing
» diffuse/pattern alopecia, that is lacking in the nude mouse seems
» plausible. This could be some other steroid, hormone, cytokine,
» neuropeptide, or an immunologically related factor.”
»
» I think that last part about the “immunologically related factor” is an
» understatement! After reading this paper, it now seems likely that the
» immune system is an even bigger factor in MPB than was previously thought.
» I personally had always assumed that the putative attack on hair follicles
» by the immune system was something that happens relatively late in the
» game, but this study is awfully compelling. But oddly enough, you see very
» little about this aspect of balding in the medical literature. Dr. Proctor,
» OTOH, has talked about it for years on alt.baldspot.
»
» So what really is the point of bringing this up in the first place, this
» issue “Of Mice and Men”?? Well, I think it can be a source of great hope
» for all of us! It proves that there exists the POTENTIAL for our poor
» follicles to regenerate completely all on their own, if only we can figure
» out how to let that happen. It appears that we may not have to wait for
» far-off and possibly risky genetic treatments, or puzzle-out all those very
» complex mesenchymal-epithelial interactions (HM, in other words), or depend
» on other high-tech treatments. We may find simpler, safer ways to do it,
» with the additional clues provided by this fascinating study.
»
» Bryan "
»
»
»
» Regards
» Pete

iNTERESTTING STUDY


#17

» » As you know Ive been talking about the immune response for a few years
» and
» » how its is one of the major factors involved in hairloss. If you can
» » reverse this factor topically and some of the other factors that it
» » triggers -I think youll be well on your way to regrowing hair!
» »
» »
» » Ive come across this extract in one of the other forums which Bryan has
» » kindly posted ( I tried to copy the link but it wouldnt post so Ive had
» to
» » copy and paste!) :
» »
» »
» »
» »
» »
» » "The study below has been cited a few times by various people on
» hairloss
» » sites over the last couple of years, but I’ve read the whole thing, and
» I
» » want to present some of the interesting details from it. First of all,
» » here’s the abstract:
» »
» » J Am Acad Dermatol. 2003 May;48(5):752-9.
» »
» » “Transplants from balding and hairy androgenetic alopecia scalp regrow
» » hair comparably well on immunodeficient mice”
» »
» » Krajcik RA, Vogelman JH, Malloy VL, Orentreich N.
» »
» » “Human hair follicles were grafted onto 2 strains of immunodeficient
» mice
» » to compare the regeneration potential of vellus (miniaturized, balding)
» and
» » terminal (hairy, nonbalding) follicles from males and a female
» exhibiting
» » pattern baldness. Each mouse had transplants of both types of follicles
» » from a single donor for direct comparison. Grafted follicles from 2
» male
» » donors resulted in nonsignificant differences in mean length (52 mm vs
» 54
» » mm) and mean diameter (99 microm vs 93 microm) at 22 weeks for hairs
» » originating from balding and hairy scalp, respectively, corresponding
» to
» » 400% versus 62% of the mean pretransplantation diameters. Follicles
» from
» » the female donor transplanted to several mice also resulted in
» » nonsignificant differences in length (43 mm vs 37 mm) for hairs from
» » balding and hairy scalp, respectively, during a period of 22 weeks. The
» » mean diameter of the originally vellus hairs increased 3-fold, whereas
» the
» » terminal hairs plateaued at approximately 50% of pretransplantation
» » diameter, resulting in a final balding hair volume double that of the
» » nonbalding hairs. This report shows that miniaturized hair follicles of
» » pattern alopecia can quickly regenerate once removed from the human
» scalp
» » and can grow as well as or better than terminal follicles from the same
» » individual.”
» »
» » The abstract gives the salient points: they found that fine vellus
» hairs
» » from balding human scalps had an EXCEPTIONAL ability to regenerate,
» when
» » transplanted onto test mice that had severe immune deficiency (they use
» » those for transplant experiments so that the mice don’t suffer rejection
» of
» » the foreign tissue). In fact, after about 5 to 6 months, transplanted
» » follicles with vellus hairs regrew to the same size as the transplanted
» » terminal hairs in one set of mice, and actually grew LARGER than the
» » terminal hairs in another set of mice (for which phenomenon they don’t
» yet
» » have any explanation)! Here’s an extended excerpt from the Discussion
» » section at the end in which they speculate about the various
» implications
» » of their findings:
» »
» » “…The phenomenon occurring in the xenograft experiments reported here
» is
» » quite different and dramatic: hypotrophic anagen and telogen hairs from
» » balding scalp exhibiting only vellus hairs in situ regenerate very
» quickly.
» » By six months, the ratio of the diameters of grafted to pretransplant
» » vellus hairs exceeds 3:1 (Fig 3). Histologic examination of
» » post-transplantation follicles from balding scalp also shows fully
» » developed anagen follicles at six months (Fig 2). The regeneration of
» » vellus follicles occurs just as quickly on male as on female mice (data
» not
» » shown); this suggests that a factor or factors other than androgen
» » withdrawal may be involved but does not necessarily rule out that
» » differences in androgen levels, availablity, or both between human
» beings
» » and mice account in part or entirely for the rapid vellus-to-terminal
» » transformation of balding follicles. For instance, the activity of the
» 5a-R
» » enzyme(s) may be greatly reduced or absent in the transplanted
» follicles,
» » thereby, limiting exposure of the follicles to DHT. The accelerated
» » transformation of vellus follicles on immunodeficient mice might
» correspond
» » to responses seen in balding men treated with oral finasteride who are
» » exceptionally good responders. However, in our clinical experience,
» females
» » with AGA, including the female in study II, frequently have normal
» androgen
» » and androgen-binding globulin levels for their age and sex. It is
» difficult
» » to argue that lower systemic androgen levels in the female mouse
» » environment (or higher in the male mice) causes the rapid regeneration
» of
» » vellus hair follicles from the human female. Therefore, the existence of
» an
» » inhibitor factor other than androgens, particularly in women showing
» » diffuse/pattern alopecia, that is lacking in the nude mouse seems
» » plausible. This could be some other steroid, hormone, cytokine,
» » neuropeptide, or an immunologically related factor.”
» »
» » I think that last part about the “immunologically related factor” is an
» » understatement! After reading this paper, it now seems likely that the
» » immune system is an even bigger factor in MPB than was previously
» thought.
» » I personally had always assumed that the putative attack on hair
» follicles
» » by the immune system was something that happens relatively late in the
» » game, but this study is awfully compelling. But oddly enough, you see
» very
» » little about this aspect of balding in the medical literature. Dr.
» Proctor,
» » OTOH, has talked about it for years on alt.baldspot.
» »
» » So what really is the point of bringing this up in the first place,
» this
» » issue “Of Mice and Men”?? Well, I think it can be a source of great
» hope
» » for all of us! It proves that there exists the POTENTIAL for our poor
» » follicles to regenerate completely all on their own, if only we can
» figure
» » out how to let that happen. It appears that we may not have to wait for
» » far-off and possibly risky genetic treatments, or puzzle-out all those
» very
» » complex mesenchymal-epithelial interactions (HM, in other words), or
» depend
» » on other high-tech treatments. We may find simpler, safer ways to do
» it,
» » with the additional clues provided by this fascinating study.
» »
» » Bryan "
» »
» »
» »
» » Regards
» » Pete
»
» iNTERESTTING STUDY

Reafirms my belief that the immune response needs to be tackled topically.

Im at a stage where I feel its easy balance our hormones ie DHT to Estradiol by using a Pygeum and SP combo.

The other area where there seems to be doubt in regards to hairloss is lifestyle /Diet - there is far too much wishy washiness.

Regards
Pete