Hair Cloning in 2004, an update in the progress of Article written exclusively for HairlossTalk and its users, Dr. Kevin McElwee provides this three-part review on the current state of hair cloning research, its history, and what you can expect to see in the coming years with this exciting new technology...
The hair follicles we are born with have to last us a lifetime. Like internal
organs, we cannot naturally generate new hair follicles in adult life. If hair
follicles are damaged or destroyed through disease or trauma, the area of affected
skin is permanently depleted of hair follicles. At least that is currently the
case, but in the same way that research is being conducted into the possibility
of organ regeneration to replace, for example, a diseased liver, scientists have
been looking at ways to regenerate hair follicles.
How Hair Cloning Works
In principle, it is possible to produce new hair follicles from certain
cells. At its simplest, a few healthy hair follicles can be excised from an individual
by biopsy. The follicles are then dissected to isolate a small ball of cells at
the base of each follicle called the dermal papilla. For the average full grown
scalp hair there are about 200-400 cells in each dermal papilla. That’s
not much, but these cells can be cultured in incubators to make several hundred
thousand cells within about 6 weeks or so. These cells can then be implanted into
bald skin where the dermal papilla cells induce new hair follicles to develop.
The process is not fully understood, but we do know that dermal papilla cells
send out chemical signals called cytokines that tell the skin to produce a new
hair follicle. A new hair follicle is made from epithelial cells, but the *development
and cycling* of the follicle is determined by dermal papilla cells. You must have
both dermal papilla cells and epithelial cells together to form a hair follicle.
Just one or the other cannot form a follicle on their own.
Re-triggering that Fetal Fun...
This process whereby dermal cells communicate with epithelial cells to produce
hair follicles occurs naturally during your fetal development. At this time, cells
destined to become dermal papilla cells, migrate through the skin dermis and start
to cluster together. The initial trigger that causes this to happen is unknown.
Each cell cluster is tells nearby epithelial cells to make a new hair follicle,
but after birth the number and distribution of dermal papilla cell structures
are all fixed in place. There is no new dermal papilla structure formation, so
there is no new hair follicle formation after birth. However, the above principle
shows that all the ingredients necessary to generate brand new follicles *are*
present in adult skin. The kicker is trying to figure out how to get these cells
to restart their communications and do what they did while you were an adorable
little fetus.
A topical Hair Cloning treatment?
It might be possible one day to cause new hair follicle formation by applying
skin with a chemical signal that triggers the resident dermal cells to return
to their embryogenic days, but such a treatment approach is not likely for a long
time. We know some of the chemical signals that might be involved, but certainly
not all of them. Products such as Lef1 or beta Catenin may be involved, but there
must be many more factors involved to induce hair follicle development that we
do not know about. Before a chemical treatment can be developed to induce new
hair follicle formation, we need to know a lot more about the mechanism of natural
hair follicle development.
(Continued on next page...)
Since we don't yet have a convenient topical liquid you can just put on your head
to kickstart new follicle development, several academic and commercial groups
based in the US, Canada, England, the Netherlands, and Japan have been looking
into the method of extracting normal hair follicles, culturing the dermal papilla
cells outside the body, and then implanting them, to induce new hair follicles.
This basic technique comes in several variations and with a variety of names,
but perhaps the most common method of referring to the hair follicle regeneration
principle is “hair or follicle cloning”. Strictly speaking, the technique
does not involve cloning in the true scientific sense (as in Dolly the sheep),
but multiple hair follicles can be produced from just one donor follicle, so it
is a sort of cloning. Others refer to “follicular neogenesis” or “multiplication”.
It is all basically the same thing.
Hair Cloning is a proven Technology
Scientists have actually known about the ability to induce new hair follicle
development by using existing hair follicles for a long time. As far back as
1944 two scientists, Lillie and Wang, were taking bits of feather follicle (which
is basically the same structure as a mammal hair follicle) and implanting them
to chicken skin to induce new hair follicles to form. In the 1960's Cohen and
Oliver showed the same could be done with rat follicles. This principle was
developed greatly by other scientists and particularly Colin Jahoda and Amanda
Reynolds who are past students of Oliver. With studies on rodents, Jahoda and
Reynolds showed that just the dermal papilla cells could be used to produce
new hair follicles, and that these cells could be cultured and then transferred
to skin to induce new hair follicles. In a paper published in the top journal
“Nature”, they showed that cells could be taken from one human donor,
(Jahoda) and implanted to another (Reynolds) and induce new hair follicle formation,
although no cell culturing was involved in this particular study. So far this
is the only study actually published to prove hair cloning would work in humans.
Since this publication, there has been a lot of interest in developing the idea
of hair and follicle cloning into a practical technique for use in the dermatology/hair
transplant clinic. Companies like Aderans (the owners of the hair transplant
chain, Bosley International) and Intercytex have set up well funded laboratories
to develop the technique. Dr's Jahoda and Reynolds continue their academic work
at Durham University in England and several other academic research scientists
have decided to jump on the bandwagon.
The Current Roadblocks with Hair Cloning
1 - Unreliable Quantities
While the principle of hair cloning is proven, turning it into a practical technique
for clinical use is fraught with problems. First, the results of implantation
can be very variable. Even if they inject the same quantity of cells, and even
if the cells are from the same donor, the number of hair follicles produced
in response is extremely unreliable. There have been unofficial reports from
two sources (Aderans/Bosley, Dr Jerry Cooley) that they have successfully induced
hair growth in humans by using cultured cells. Unfortunately the success rate
stated by both sources was poor. Implantation of cultured cells to volunteers
by Aderans/Bosley produced just 2 hairs in a single individual. Dr Jerry Cooley
implanted cultured cells into himself at fifteen different sites but only managed
to promote one hair follicle to grow.
2 - Unreliable Angles
Second, the new hair follicles induced in studies using rats or mice are usually
disorientated. Natural hair follicles grow hair with a “grain”,
so on your scalp your hair grows in whirl pattern (usually clockwise) about
the vertex. On your lower legs your hair grows down towards your feet etc. With
hair follicles induced in hair cloning studies on rodents, the follicles can
grow hair at all sorts of angles. This gives a cosmetically “scruffy”
appearance.
3 - Uneven Distribution / Patchy Growth
Third, natural hair follicles are evenly distributed over the skin, but in rodent
studies hair follicles induced by hair cloning do not have an even distribution
over the skin – there can be clumps of hair growth. Again, the cosmetic
appearance of this clumpy growth is generally unacceptable.
For hair cloning to become a practical and popular treatment, all these problems
must be overcome.
For Hair Cloning to work, researchers need to be
able to (1) produce a consistent number of hair follicles
for a given number of injected dermal papilla cells (2)
figure out how to control the angle at which the new follicles grow and (3)
produce a consistent level of density over the treated area. Currently, these
are the 3 main roadblocks to successful hair cloning.
(Continued on next page...)
New Study of Dermal Papilla & Hair Growth
Two very recent studies from academic research groups have added new information
to the debate on the future of hair cloning. The first paper by Paus and colleagues
in Hamburg, Germany and Bradford England, shows that the ball of cells necessary
to make new follicles do not originate only in the dermal papilla. By analyzing
follicles in different stages of the hair growth cycle, they found that the dermal
papilla structure is filled with cells that have migrated from an adjacent structure
around the hair follicle called the “dermal sheath”.
The dermal sheath is an outer sleeve of cells around the epithelial component
of the hair fiber-producing part of the hair follicle. Clear as mud? :)
In other words, cells in the dermal sheath were previously thought to only play
a minor role, mostly as physical support to the hair follicle. This recent study
has shown that cells multiply in the lower dermal sheath and then migrate into
the dermal papilla at the start of a new hair growth cycle. At the end of the
hair growth cycle the cells migrate out again either back into the dermal sheath
or out into the dermis.
This might be one explanation as to how androgenetic alopecia develops. If at
the end of each growth cycle the dermal papilla cells migrate away from the follicle
never to return, then the dermal papilla structure may get progressively smaller
with each growth cycle - but this is a story for another time.
Figure 1 above: (a)
Cross-section view of a hair follicle in growth phase (anagen) and the bulb region
(b) the same follicle with the dermal component outlined
with an dotted line. The hair follicle dermal component can be subdivided into
at least three parts based on morphology and the ability of cells to induce new
hair follicles (c) The dermal papilla (DP) sits at
the base of the hair follicle in a pear shape structure. The DP is fed by cells
of the lower dermal sheath called the dermal sheath “cup” (DSC). The
cells of the dermal sheath (DS) away from the hair follicle bulb have no apparent
ability to induce new hair follicle development.
How this Study relates to Hair Cloning
The size of the dermal papilla is known to directly dictate the size of the
hair fiber produced. A big papilla promotes the growth of a big hair fiber.
For the purposes of understanding hair cloning, the study shows that the dermal
sheath plays an active role in determining the size of the dermal papilla. The
dermal sheath provides the cells. The Dermal Papilla is created with these cells.
The two together define the size of the hair fiber produced, and how long that
hair will stay in growth phase. This is very important for hair cloning. It
shows that to make big, healthy new hair follicles with hair cloning, you need
to use cells from a big, healthy donor hair follicle. The cells from the donor
follicle apparently retain the instructions for a big follicle and transfer
this information to the new follicle in hair cloning.
The second paper from Marburg Germany takes these observations a step further.
In these studies the scientists used cells that contained a green fluorescent
protein tag. Under ultra violet (UV) light the cells fluoresce green and this
enables the scientists to follow where the cells go and what they do over time.
The scientists took dermal papilla cells and dermal sheath cells, cultured them,
and then injected them into normal mouse ears and mouse feet.
(Continued on next page...)
Alkaline Phosphatase
Mouse feet do not, in general, have hair follicles in them, just like
human palms and soles. However, mouse ears, like humans ears, are covered in
tiny hair follicles that produce tiny hair fibers (vellus hair fibers in humans).
After about 3 months, the scientists observed visible new hair growth from the
injected skin, both with dermal papilla and cells form the lower dermal sheath,
next to the dermal papilla, but not the upper dermal sheath. This showed that
both cell types, although they came from different structural components of
the hair follicle, were functionally similar - both cell populations could induce
new hair follicle formation. The scientists also demonstrated that the cells
with the ability to induce hair growth were alkaline phosphatase positive. Alkaline
phosphatase itself probably has nothing to do with the ability to induce hair
growth, but its expression is potentially a useful method of quality control.
Conclusion? Those cells with alkaline phosphatase positive expression are the
ones you want to take, culture, and transplant. Cells that are alkaline phosphatase
negative do not seem to promote new hair growth and should be discarded. This
may help improve the success rate with hair cloning.
Injected cells merging with existing cells
At 3 and 6 months post cell injection, the scientists shone UV light on the mouse
ear and foot tissue. They could see that the implanted fluorescent cells were
found within hair follicles and the cells were in the dermal sheath and dermal
papilla structures. This suggested the both cell populations were capable of inducing
brand new hair follicles to develop. That is not so surprising given the previous
work in this field by Jahoda and others. However, what was more intriguing for
understanding hair cloning, was that in mouse ears there were “chimeric”
hair follicles with dermal papilla and dermal sheath structures containing both
fluorescent and non-fluorescent cells combined. The scientists suggested that
this was an indicator that the injected fluorescent cells had migrated in and
integrated themselves into the tiny natural hair follicles already present in
the ears. The new cells had apparently altered the size and growth cycle of the
tiny hair follicles to make them much bigger and to make them grow for longer
which in turn produced bigger hair fibers.
Fig 2 above: Cultured dermal papilla cells injected into
a mouse ear induce new hair follicles and modify natural hair follicles already
present to yield tufts of long hair growth 4 months after injection.
Using injected cells to reverse Miniaturization?
This observation makes several important points in terms of using hair
cloning to treat androgenetic alopecia. If cells can be implanted that will integrate
with resident hair follicles, then men and women in the early stages of androgenetic
alopecia could be treated. Hair follicles in the process of miniaturization could
be boosted with implanted cells to force them back into a full sized, terminal
growth state. By exploiting the resident hair follicle structures as a guide for
the implanted cells, the problems of erratic follicle orientation and distribution
over the skin, seen in hair cloning studies so far, could be resolved. The damaged,
small, natural hair follicles would provide the distribution pattern and angle
of orientation, while the injected dermal papilla cells would contribute the characteristics
of large, terminal hair follicles. So those in the early stages of baldness with
just a little thinning, could significantly benefit from hair cloning. In theory,
young men and women in families where the androgenetic alopecia trait is strong
and who are likely to develop androgenetic alopecia could be injected with cells
in advance of overt hair loss and need never develop any alopecia.
Even men in the late stages of androgenetic alopecia with extensive baldness might
still benefit from this observation. Even in apparently bald skin, there are usually
tiny vellus hair follicles still present. It is possible these follicles still
retain a “memory” of what they once were and their old growth patterns
as terminal hair follicles. If so, it may be possible to implant cells such that
they integrate with the vellus hair follicles and produce a cosmetically acceptable
result even for extensively bald men and women. It remains to be seen whether
the perceived problems of follicle orientation and distribution identified in
scientific studies with rodents actually prove founded when transferred to the
bald human scalp. The process of androgenetic alopecia with gradual miniaturization
of hair follicles may actually be ideal for the hair cloning technique to work.
The Migrated might continute to Migrate...
Both studies reinforce the fact that the cultured dermal papilla cells, and also
lower dermal sheath cells, retain the characteristics of the donor hair follicle.
There has been some concern that the property of large hair follicle induction
that is transferred with the implanted cells would gradually dissipate over time.
Most recently, in the December 2003 issue of the Journal for Investigative Dermatology,
Dr Jahoda has expressed this fear in a commentary on both the above papers. The
observation by Paus et al, that cells can disperse from the dermal papilla at
the end of the hair cycle raise the question of whether the implanted cells of
hair cloning might eventually migrate away leading to a progressive redevelopment
of the alopecia. This is an important issue that remains to be resolved. Rodent
models have shown hair growth induced by hair cloning to last for at least 18
months with no significant change, but the naturally short life span of rats and
mice (around 2 years) means that scientists will not be able to claim induced
hair growth survival much beyond this time span. The answer to this question probably
won’t be elucidated until long term studies are conducted directly on humans.
Overall then, good progress is being made with hair cloning, but there is much
more work to be done before hair cloning can become a routine procedure that yields
consistent results in humans.
References:
Tobin DJ, Gunin A, Magerl M, Handijski B, Paus R.
Plasticity and cytokinetic dynamics of the hair follicle mesenchyme: implications
for hair growth control. J Invest Dermatol. 2003 Jun;120(6):895-904.
McElwee KJ, Kissling S, Wenzel E, Huth A, Hoffmann
R. Cultured peribulbar dermal sheath cells can induce hair follicle development
and contribute to the dermal sheath and dermal papilla. J Invest Dermatol. 2003
Dec;121(6):1267-75.
Jahoda CA. Cell Movement in the Hair Follicle Dermis
- More Than a Two-Way Street? J Invest Dermatol. 2003 Dec;121(6):IX-XI.
HLT
The hair follicles we are born with have to last us a lifetime. Like internal
organs, we cannot naturally generate new hair follicles in adult life. If hair
follicles are damaged or destroyed through disease or trauma, the area of affected
skin is permanently depleted of hair follicles. At least that is currently the
case, but in the same way that research is being conducted into the possibility
of organ regeneration to replace, for example, a diseased liver, scientists have
been looking at ways to regenerate hair follicles.
How Hair Cloning Works
In principle, it is possible to produce new hair follicles from certain
cells. At its simplest, a few healthy hair follicles can be excised from an individual
by biopsy. The follicles are then dissected to isolate a small ball of cells at
the base of each follicle called the dermal papilla. For the average full grown
scalp hair there are about 200-400 cells in each dermal papilla. That’s
not much, but these cells can be cultured in incubators to make several hundred
thousand cells within about 6 weeks or so. These cells can then be implanted into
bald skin where the dermal papilla cells induce new hair follicles to develop.
The process is not fully understood, but we do know that dermal papilla cells
send out chemical signals called cytokines that tell the skin to produce a new
hair follicle. A new hair follicle is made from epithelial cells, but the *development
and cycling* of the follicle is determined by dermal papilla cells. You must have
both dermal papilla cells and epithelial cells together to form a hair follicle.
Just one or the other cannot form a follicle on their own.
Re-triggering that Fetal Fun...
This process whereby dermal cells communicate with epithelial cells to produce
hair follicles occurs naturally during your fetal development. At this time, cells
destined to become dermal papilla cells, migrate through the skin dermis and start
to cluster together. The initial trigger that causes this to happen is unknown.
Each cell cluster is tells nearby epithelial cells to make a new hair follicle,
but after birth the number and distribution of dermal papilla cell structures
are all fixed in place. There is no new dermal papilla structure formation, so
there is no new hair follicle formation after birth. However, the above principle
shows that all the ingredients necessary to generate brand new follicles *are*
present in adult skin. The kicker is trying to figure out how to get these cells
to restart their communications and do what they did while you were an adorable
little fetus.
A topical Hair Cloning treatment?
It might be possible one day to cause new hair follicle formation by applying
skin with a chemical signal that triggers the resident dermal cells to return
to their embryogenic days, but such a treatment approach is not likely for a long
time. We know some of the chemical signals that might be involved, but certainly
not all of them. Products such as Lef1 or beta Catenin may be involved, but there
must be many more factors involved to induce hair follicle development that we
do not know about. Before a chemical treatment can be developed to induce new
hair follicle formation, we need to know a lot more about the mechanism of natural
hair follicle development.
(Continued on next page...)
Since we don't yet have a convenient topical liquid you can just put on your head
to kickstart new follicle development, several academic and commercial groups
based in the US, Canada, England, the Netherlands, and Japan have been looking
into the method of extracting normal hair follicles, culturing the dermal papilla
cells outside the body, and then implanting them, to induce new hair follicles.
This basic technique comes in several variations and with a variety of names,
but perhaps the most common method of referring to the hair follicle regeneration
principle is “hair or follicle cloning”. Strictly speaking, the technique
does not involve cloning in the true scientific sense (as in Dolly the sheep),
but multiple hair follicles can be produced from just one donor follicle, so it
is a sort of cloning. Others refer to “follicular neogenesis” or “multiplication”.
It is all basically the same thing.
Hair Cloning is a proven Technology
Scientists have actually known about the ability to induce new hair follicle
development by using existing hair follicles for a long time. As far back as
1944 two scientists, Lillie and Wang, were taking bits of feather follicle (which
is basically the same structure as a mammal hair follicle) and implanting them
to chicken skin to induce new hair follicles to form. In the 1960's Cohen and
Oliver showed the same could be done with rat follicles. This principle was
developed greatly by other scientists and particularly Colin Jahoda and Amanda
Reynolds who are past students of Oliver. With studies on rodents, Jahoda and
Reynolds showed that just the dermal papilla cells could be used to produce
new hair follicles, and that these cells could be cultured and then transferred
to skin to induce new hair follicles. In a paper published in the top journal
“Nature”, they showed that cells could be taken from one human donor,
(Jahoda) and implanted to another (Reynolds) and induce new hair follicle formation,
although no cell culturing was involved in this particular study. So far this
is the only study actually published to prove hair cloning would work in humans.
Since this publication, there has been a lot of interest in developing the idea
of hair and follicle cloning into a practical technique for use in the dermatology/hair
transplant clinic. Companies like Aderans (the owners of the hair transplant
chain, Bosley International) and Intercytex have set up well funded laboratories
to develop the technique. Dr's Jahoda and Reynolds continue their academic work
at Durham University in England and several other academic research scientists
have decided to jump on the bandwagon.
The Current Roadblocks with Hair Cloning
1 - Unreliable Quantities
While the principle of hair cloning is proven, turning it into a practical technique
for clinical use is fraught with problems. First, the results of implantation
can be very variable. Even if they inject the same quantity of cells, and even
if the cells are from the same donor, the number of hair follicles produced
in response is extremely unreliable. There have been unofficial reports from
two sources (Aderans/Bosley, Dr Jerry Cooley) that they have successfully induced
hair growth in humans by using cultured cells. Unfortunately the success rate
stated by both sources was poor. Implantation of cultured cells to volunteers
by Aderans/Bosley produced just 2 hairs in a single individual. Dr Jerry Cooley
implanted cultured cells into himself at fifteen different sites but only managed
to promote one hair follicle to grow.
2 - Unreliable Angles
Second, the new hair follicles induced in studies using rats or mice are usually
disorientated. Natural hair follicles grow hair with a “grain”,
so on your scalp your hair grows in whirl pattern (usually clockwise) about
the vertex. On your lower legs your hair grows down towards your feet etc. With
hair follicles induced in hair cloning studies on rodents, the follicles can
grow hair at all sorts of angles. This gives a cosmetically “scruffy”
appearance.
3 - Uneven Distribution / Patchy Growth
Third, natural hair follicles are evenly distributed over the skin, but in rodent
studies hair follicles induced by hair cloning do not have an even distribution
over the skin – there can be clumps of hair growth. Again, the cosmetic
appearance of this clumpy growth is generally unacceptable.
For hair cloning to become a practical and popular treatment, all these problems
must be overcome.
For Hair Cloning to work, researchers need to be
able to (1) produce a consistent number of hair follicles
for a given number of injected dermal papilla cells (2)
figure out how to control the angle at which the new follicles grow and (3)
produce a consistent level of density over the treated area. Currently, these
are the 3 main roadblocks to successful hair cloning.
(Continued on next page...)
New Study of Dermal Papilla & Hair Growth
 |
Two very recent studies from academic research groups have added new information
to the debate on the future of hair cloning. The first paper by Paus and colleagues
in Hamburg, Germany and Bradford England, shows that the ball of cells necessary
to make new follicles do not originate only in the dermal papilla. By analyzing
follicles in different stages of the hair growth cycle, they found that the dermal
papilla structure is filled with cells that have migrated from an adjacent structure
around the hair follicle called the “dermal sheath”.
The dermal sheath is an outer sleeve of cells around the epithelial component
of the hair fiber-producing part of the hair follicle. Clear as mud? :)
In other words, cells in the dermal sheath were previously thought to only play
a minor role, mostly as physical support to the hair follicle. This recent study
has shown that cells multiply in the lower dermal sheath and then migrate into
the dermal papilla at the start of a new hair growth cycle. At the end of the
hair growth cycle the cells migrate out again either back into the dermal sheath
or out into the dermis.
This might be one explanation as to how androgenetic alopecia develops. If at
the end of each growth cycle the dermal papilla cells migrate away from the follicle
never to return, then the dermal papilla structure may get progressively smaller
with each growth cycle - but this is a story for another time.
Figure 1 above: (a)
Cross-section view of a hair follicle in growth phase (anagen) and the bulb region
(b) the same follicle with the dermal component outlined
with an dotted line. The hair follicle dermal component can be subdivided into
at least three parts based on morphology and the ability of cells to induce new
hair follicles (c) The dermal papilla (DP) sits at
the base of the hair follicle in a pear shape structure. The DP is fed by cells
of the lower dermal sheath called the dermal sheath “cup” (DSC). The
cells of the dermal sheath (DS) away from the hair follicle bulb have no apparent
ability to induce new hair follicle development.
How this Study relates to Hair Cloning
The size of the dermal papilla is known to directly dictate the size of the
hair fiber produced. A big papilla promotes the growth of a big hair fiber.
For the purposes of understanding hair cloning, the study shows that the dermal
sheath plays an active role in determining the size of the dermal papilla. The
dermal sheath provides the cells. The Dermal Papilla is created with these cells.
The two together define the size of the hair fiber produced, and how long that
hair will stay in growth phase. This is very important for hair cloning. It
shows that to make big, healthy new hair follicles with hair cloning, you need
to use cells from a big, healthy donor hair follicle. The cells from the donor
follicle apparently retain the instructions for a big follicle and transfer
this information to the new follicle in hair cloning.
The second paper from Marburg Germany takes these observations a step further.
In these studies the scientists used cells that contained a green fluorescent
protein tag. Under ultra violet (UV) light the cells fluoresce green and this
enables the scientists to follow where the cells go and what they do over time.
The scientists took dermal papilla cells and dermal sheath cells, cultured them,
and then injected them into normal mouse ears and mouse feet.
(Continued on next page...)
Alkaline Phosphatase
Mouse feet do not, in general, have hair follicles in them, just like
human palms and soles. However, mouse ears, like humans ears, are covered in
tiny hair follicles that produce tiny hair fibers (vellus hair fibers in humans).
After about 3 months, the scientists observed visible new hair growth from the
injected skin, both with dermal papilla and cells form the lower dermal sheath,
next to the dermal papilla, but not the upper dermal sheath. This showed that
both cell types, although they came from different structural components of
the hair follicle, were functionally similar - both cell populations could induce
new hair follicle formation. The scientists also demonstrated that the cells
with the ability to induce hair growth were alkaline phosphatase positive. Alkaline
phosphatase itself probably has nothing to do with the ability to induce hair
growth, but its expression is potentially a useful method of quality control.
Conclusion? Those cells with alkaline phosphatase positive expression are the
ones you want to take, culture, and transplant. Cells that are alkaline phosphatase
negative do not seem to promote new hair growth and should be discarded. This
may help improve the success rate with hair cloning.
Injected cells merging with existing cells
 |
At 3 and 6 months post cell injection, the scientists shone UV light on the mouse
ear and foot tissue. They could see that the implanted fluorescent cells were
found within hair follicles and the cells were in the dermal sheath and dermal
papilla structures. This suggested the both cell populations were capable of inducing
brand new hair follicles to develop. That is not so surprising given the previous
work in this field by Jahoda and others. However, what was more intriguing for
understanding hair cloning, was that in mouse ears there were “chimeric”
hair follicles with dermal papilla and dermal sheath structures containing both
fluorescent and non-fluorescent cells combined. The scientists suggested that
this was an indicator that the injected fluorescent cells had migrated in and
integrated themselves into the tiny natural hair follicles already present in
the ears. The new cells had apparently altered the size and growth cycle of the
tiny hair follicles to make them much bigger and to make them grow for longer
which in turn produced bigger hair fibers.
Fig 2 above: Cultured dermal papilla cells injected into
a mouse ear induce new hair follicles and modify natural hair follicles already
present to yield tufts of long hair growth 4 months after injection.
Using injected cells to reverse Miniaturization?
This observation makes several important points in terms of using hair
cloning to treat androgenetic alopecia. If cells can be implanted that will integrate
with resident hair follicles, then men and women in the early stages of androgenetic
alopecia could be treated. Hair follicles in the process of miniaturization could
be boosted with implanted cells to force them back into a full sized, terminal
growth state. By exploiting the resident hair follicle structures as a guide for
the implanted cells, the problems of erratic follicle orientation and distribution
over the skin, seen in hair cloning studies so far, could be resolved. The damaged,
small, natural hair follicles would provide the distribution pattern and angle
of orientation, while the injected dermal papilla cells would contribute the characteristics
of large, terminal hair follicles. So those in the early stages of baldness with
just a little thinning, could significantly benefit from hair cloning. In theory,
young men and women in families where the androgenetic alopecia trait is strong
and who are likely to develop androgenetic alopecia could be injected with cells
in advance of overt hair loss and need never develop any alopecia.
Even men in the late stages of androgenetic alopecia with extensive baldness might
still benefit from this observation. Even in apparently bald skin, there are usually
tiny vellus hair follicles still present. It is possible these follicles still
retain a “memory” of what they once were and their old growth patterns
as terminal hair follicles. If so, it may be possible to implant cells such that
they integrate with the vellus hair follicles and produce a cosmetically acceptable
result even for extensively bald men and women. It remains to be seen whether
the perceived problems of follicle orientation and distribution identified in
scientific studies with rodents actually prove founded when transferred to the
bald human scalp. The process of androgenetic alopecia with gradual miniaturization
of hair follicles may actually be ideal for the hair cloning technique to work.
The Migrated might continute to Migrate...
Both studies reinforce the fact that the cultured dermal papilla cells, and also
lower dermal sheath cells, retain the characteristics of the donor hair follicle.
There has been some concern that the property of large hair follicle induction
that is transferred with the implanted cells would gradually dissipate over time.
Most recently, in the December 2003 issue of the Journal for Investigative Dermatology,
Dr Jahoda has expressed this fear in a commentary on both the above papers. The
observation by Paus et al, that cells can disperse from the dermal papilla at
the end of the hair cycle raise the question of whether the implanted cells of
hair cloning might eventually migrate away leading to a progressive redevelopment
of the alopecia. This is an important issue that remains to be resolved. Rodent
models have shown hair growth induced by hair cloning to last for at least 18
months with no significant change, but the naturally short life span of rats and
mice (around 2 years) means that scientists will not be able to claim induced
hair growth survival much beyond this time span. The answer to this question probably
won’t be elucidated until long term studies are conducted directly on humans.
Overall then, good progress is being made with hair cloning, but there is much
more work to be done before hair cloning can become a routine procedure that yields
consistent results in humans.
References:
Tobin DJ, Gunin A, Magerl M, Handijski B, Paus R.
Plasticity and cytokinetic dynamics of the hair follicle mesenchyme: implications
for hair growth control. J Invest Dermatol. 2003 Jun;120(6):895-904.
McElwee KJ, Kissling S, Wenzel E, Huth A, Hoffmann
R. Cultured peribulbar dermal sheath cells can induce hair follicle development
and contribute to the dermal sheath and dermal papilla. J Invest Dermatol. 2003
Dec;121(6):1267-75.
Jahoda CA. Cell Movement in the Hair Follicle Dermis
- More Than a Two-Way Street? J Invest Dermatol. 2003 Dec;121(6):IX-XI.
HLT