Part three of our hair cloning article delves into some new studies and recent findings that showed possible application of injected cells to actually strengthen and regenerate dying hairs. The significance? A new treatment for male and female pattern baldness...
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.
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.
