Organ Regeneration Based on Developmental Biology

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6.7.3 Reproduction of the Cooperative Function

of the Bioengineered Hair Follicle

The peripheral nervous system has essential roles in organ function and the percep-
tion of noxious stimuli, such as pain and mechanical stress (Grant et al. 2009 ; Peters
et al. 2006 ; Jahoda and Christiano 2011 ). Restoration of the nervous system is thus
a critical issue that must be addressed by organ replacement regenerative therapy
(Toyoshima et al. 2012 ; Asakawa et al. 2012 ; Tezuka et al. 2016 ). In the hair follicle,
the follicles, pelage, and vibrissae achieve piloerection using the surrounding arrec-
tor pili muscle through activation of the sympathetic nerves and also function as a
sensory organ  (Peters et  al. 2001 , 2006 ; Sato et  al. 2012 ). Toyoshima et  al. also
demonstrated that the nerve fibers and muscles can connect autonomously to the
pelage and vibrissa follicle and that the bioengineered follicles exhibit piloerection.
These results suggest that the transplantation of a bioengineered hair follicle germ
can restore natural hair function and reestablish the cooperation between the follicle
and the surrounding recipient muscles and nerves (Toyoshima et al. 2012 ; Asakawa
et al. 2012 ; Tezuka et al. 2016 ) (Fig. 6.6). Thus, transplantation of the bioengineered
hair follicle germ may be applicable for the future surgical treatment of alopecia
(Toyoshima et al. 2012 ).

Proximal hair

matrix region

(PHM)

DP

Bio-germ

(Bulge/DP)

+PHM cells

First hair growth

Bioengineered hairs

306 days

Bulge

region

Bio-germ

(Bulge/DP)

Fig. 6.5 Hair pigmentation of the bioengineered vibrissae by cell combinations with bioengi-
neered vibrissa follicle cell components. The bioengineered vibrissa follicle germ, which was
reconstituted between the bulge epithelial stem cells and the primary cultured DP cells (upper),
was combined with the proximal region of the hair matrix (+PHM; lower). Unpigmented and pig-
mented bioengineered hairs at the first growth phase and at 306 days after transplantation are
shown in right photographs, respectively. Bars, 1 mm

K.-e. Toyoshima and T. Tsuji