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Testrapport Follicular Unit Multiplication:
Is it Possible to Harvest an Unlimeted Donor Supply?
Ergin Er, MD, Melike Kulahci, MD, Emirali Hamiloglu, MD Istanbul, Turkey
*This study was supported by research grant from the ISHRS.
Introduction:
The limitations of the donor area reserve is a significant problem facing hair restoration surgeons.
As the degree of baldness advances, the number of grafts available may not be sufficient for a satisfactory result. Methods for increasing the potential donor supply, such as stem cell implantation and in vitro hair follicle,
regeneration are still under investigation. Another recent advance is follicular unit extraction (FUE), which may theoretically permit harvesting of an increased number of follicular groups from the scalp and other body areas.
During our successive FUE sessions, we have observed new hair growth from the scar of previously extracted sites.
This finding directed us to pursue a kind of in-vivo multiplication such that the donor site can be harvested several
times. Several authors have demonstrated that follicular epithelial stem cells are located in the bulbar region as well
as the bulge area. In 1995 Kim et al.1 and in 1999 Reynolds et al.2 reported that outer root sheath cells cultured
from different parts of a hair follicle could regenerate into differentiated hair follicles. Based on Dr. Kim’s and
Dr. Reynold’s studies, we hypothesized that transecting the hair follicle at different levels and leaving the base of
each follicle attached and in situ would permit a viable donor graft to be generated from one donor hair but it
would also allow for hair regrowth from the remaining part of each follicle in the donor site. Therefore, the number
of donor hairs available from a patient would increase and perhaps become unlimited.
Since transection is a common problem with FUE, establishing the growth potential of these fragments is of great
interest. In this clinical study, we transplanted different parts of bisected hair follicles, harvested using the FUE -
technique, from the donor site. Growth was then assessed both at the recipient site and the donor site.
Material and Methods:
Using the FUE technique, normal human occipital scalp hair follicles were obtained from 5 healthy male patients.
A total of 45 hair follicles were isolated from each patient. These follicles were divided into three groups: Group A
(N=15): The upper one-third of the follicles were extracted from the donor site, leaving the remaining two-thirds
of each follicle intact and in situ. Group B (N=15): The upper one-half of the follicles was extracted, leaving the
remaining lower half of each follicle intact and in situ. Group C (N=15): The upper two-thirds of the follicles were extracted, leaving the lower one-third of each follicle intact and in situ. The recipient area was divided into three
1cm2 boxes using permanent tattoos, and extracted follicles from each group were placed into slits within these
boxes. Hair counts and hair shaft diameter was measured at 1 year by an independent third party.
Results:
A total of 225 grafts were extracted and planted for all three levels of transection, and both donor and recipient
sites were evaluated at 1 year for growth. For grafts transected at the upper one-third level, recipient growth
varied from 13.3% to 26.6% (mean 20%), while donor regrowth varied from 66.6% to 93.3% (mean 84%). For
grafts transected at the upper one-half level, recipient growth varied from 13.3% to 40% (mean 29.3%), while
donor regrowth varied from 53.3% to 86.6% (mean 68%). For grafts transected at the upper two-thirds level,
recipient growth varied from 33.3% to 53.3% (mean 41.3%), while donor regrowth varied from 46.6% to 80%
(mean 53.3%). Growth rates are summarized in the chart below.
Discussion:
The hair follicle is a complex structure. It contains stem cells that govern the rate of cell loss and the regeneration
of the hair during its life cycle.4 These stem cells are not only located at the bulb but also at the outer sheath
close to the erector pili muscle in the “bulge” area located near the mid portion of the follicle.5,6 Therefore,
theoretically, each half of the follicle should contain a stem cell reservoir allowing for new shaft production and
hair growth, and therefore follicle duplication. Recently, Rochat and Kobayashi confirmed the bulge hypothesis
by isolating keratinocyte colony-forming cells from human hair follicles.7 They transected hair follicles at the level immediately below the bulge area. The lower half of the follicle had the same growth rate as the intact follicle but
the upper half exhibited a reduced shaft production capacity, suggesting that it still contained some follicular stem
cells. This study showed that the upper half of the follicle could regenerate independent from the bulb. In our study
we observed similar results with a growth rate of 29.3% in the upper half of the follicles after 1 year. But the
regrowth rate was 68% at the donor site during this period, which is low when compared to transplanting an intact
follicle. This result emphasizes the importance of the outer sheath cells for regeneration of the hair follicle.
Oliver et al. showed that rat vibrissae could still regenerate after removing the lowest one-third of the follicle.8
Similarly, Inaba et al., Kim, and Choi proved that grafted hair follicles could regenerate after removal from the
bulb.2,9 In our study, we observed 20% of the upper one-third and 41.3% of the upper two-thirds of a hair,
follicle could regenerate as a new follicle after transplantation. These results demonstrate that as the transection
level goes lower and the number of outer root sheath cells included in the graft increases, the survival rate will also increase. This data also supports the bulge hypothesis, which indicates that stem cell migration begins in the
upper outer root sheath and moves downward through the bulb area. Therefore, it is logical to include both stem cell locations and as much outer sheath as possible to increase the graft yield after the transplantation.
The most important problem in FUE procedures is the unacceptable levels of transection in some patients.
Our study showed that these transected follicles can still grow at the recipient site. However, the degree of
recipient growth depends on the level of transection. In addition, even if the upper two-thirds of the follicle is transplanted, emerging follicles at the recipient site are thinner than the original ones and therefore cannot cover
the recipient site sufficiently. Although bulge area stem cells can regenerate a new follicle, without the bulb the
new follicle will not have the original caliber. Placing these transected grafts may therefore not be in the patient’s
best interest. If transected grafts must be placed, selecting those grafts containing at least the upper half of the
follicle and placing at a high density should be considered by the surgeon.
Extracting intact grafts from the same donor site after regrowth also proved very difficult, as the weakened skin at
these sites caused the punch to suddenly penetrate into the skin.
In summary, our study did not support the concept of unlimited or repetitive donor harvesting using FUE.
Follicular unit extraction is a minimally invasive surgical procedure that has some advantages to classical strip
harvesting, but the high rate of transection remains an important drawback. To our knowledge, our clinical study
is the first study that compares bisected hair follicle growth and donor regrowth for individual follicles obtained
by FUE. The survival and growth rate of transversely sectioned human hair follicles directly depends on the level of transection. However, we don’t recommend routine transplantation of the sectioned parts due to low growth rates
and diminished hair shaft caliber.
References:
- Rassman WR, et al. Follicular unit extraction: minimally invasive surgery for hair transplantation.
Dermatol Surg 2002; 28: 720–728.
2. Kim JC, Choi YC. Regrowth of grafted human scalp hair after removal of the bulb. Dermatol Surg 1995;
21(4): 312–313.
3. Reynolds AJ, et al. Trans-gender induction of hair follicles. Nature 4 November 1999; 402(6757): 33–34.
4. Gho CG, et al. Human follicular stem cells: their presence in plucked hair and follicular cell culture.
Br J Dermatol 2004; 150(5): 860–868.
5. de Viragh PA, Meuli M. Human scalp hair follicle development from birth to adulthood: statistical study with
special regard to putative stem cells in the bulge and proliferating cells in the matrix. Arch Dermatol Res 1995;
287(3-4): 279–284.
6. Raposio E, et al. Follicular bisection in hair transplantation surgery: an in vitro model. Plast Reconstr Surg 1998
(July); 102(1): 221–226.
7. Rochat A, Kobayashi K, Barrandon Y. Location of stem cells of human hair follicles by clonal analysis. Cell 25
March 1994; 76(6): 1063–1073.
8. Oliver RF. Whisker growth after removal of the dermal papilla and lengths of follicle in the hooded rat. J Embryol
Exp Morphol 1966 (June); 15(3): 331–347.
9. Inaba M, Anthony J, McKinstry C. Histologic study of the regeneration of axillary hair after removal with
subcutaneous tissue shaver. J Invest Dermatol 1979; 72(5): 224–231.
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