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embryonic hair germ of murine vibrissae, can ectopically regenerate a bioengi-
neered hair follicle producing a hair shaft under the kidney capsule (Nakao et al.
2007 ; Asakawa et al. 2012 ) (Fig. 6.2c).
6.7.1 Hair Follicle Regeneration by Intracutaneous
Transplantation of the Bioengineered Hair Follicle Germ
It is essential to evaluate whether the bioengineered hair follicle germ can develop
into a structurally proper bioengineered hair follicle in the adult intracutaneous
environment to provide fully functional hair organ regeneration, including hair
eruption growth, hair cycles, and connections with surrounding tissues, based on the
functional regeneration of stem cell niches (Toyoshima et al. 2012 ). Toyoshima
et al. successfully demonstrated that the bioengineered hair follicle germ was
reconstituted with considerably small number of adult murine vibrissa hair
follicle- derived epithelial stem cells (10^4 cells) and cultured dermal papilla cells
(3 × 10^3 cells) using an organ germ method and regenerated the hair follicle in the
murine skin environment through the novel development of the intracutaneous
transplantation method, which was based on the FUT surgical operation procedure
for ready availability for clinical application (Toyoshima et al. 2012 ; Tezuka et al.
2016 ) (Fig. 6.2c and 6.3).
Surgical specialists in FUT therapy generally dissect normal hair follicles that
maintain their structural integrity in an epithelium of the hair opening and hair shaft
and then translocationally engraft them into the bold region by maintaining the
external direction so that it protrudes from the skin surface to achieve a high engraft-
ment efficiency and no significant adverse events, such as serious infectious disease
and postoperative cyst formation (Toyoshima et al. 2012 ; Tezuka et al. 2016 ). To
prevent posttransplant cyst formation by the rapid closing between the host skin
epithelium and the bioengineered hair follicle germ, as a guide for the direction
of the infundibulum, an inter-epithelial tissue-connecting nylon thread is highly
effective for the accurate arrangement of the newly formed hair pore of the bioengi-
neered hair follicle to the surrounding host skin epithelium (Toyoshima et al. 2012 ;
Tezuka et al. 2016 ) (Fig. 6.3). In cases of bioengineered vibrissa follicles, the bio-
engineered hair shafts erupt at a resulting frequency of 74% at 21 days after engraft-
ment and are almost unpigmented (Fig. 6.3). These results raise the possibility not
only of hair organ regeneration in the adult skin environment but also reestablish-
ment of the connections between the bioengineered hair follicle and the recipient
skin, similar to the results obtained using FUT.
It is preferable for a clinically applicable hair regeneration therapy to utilize
autologous FUT therapy, which is the most popular and effective surgical cure for
various types of hair loss. The density, area, and direction of grafting of follicular
units can be practically controlled in ranges to achieve therapeutic goals (Toyoshima
et al. 2012 ). In the preparation of bioengineered follicle germs, it has been indicated
K.-e. Toyoshima and T. Tsuji