Organ Regeneration Based on Developmental Biology

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organization of epithelial and mesenchymal cells in a 3D stem cell culture (Nakao
et al. 2007 ; Ikeda et al. 2009 ) (Fig. 6.2c). The bioengineered organ germs reconsti-
tuted using the organ germ method could regenerate the fully functional bioengi-
neered hair follicles in vivo. Hair regeneration has been successfully demonstrated
by intracutaneous transplantation of a bioengineered pelage and vibrissa hair folli-
cle germ or ectopically regenerated mature hair follicle, which was regenerated with

Newly Induced

hair

Mesenchymalcell

replacement

Adult hair follicle

a

b

c

DP/DS cells

Bioengineered hair

follicle germ

Adult hair stem

cells

Cultured DP cells

Bulge epithelial cells

Orthotopichair

regeneration

Newly induced

skin or cyst with

hairs

Mesenchymal

Epithelial

Embryonic skin

cells

Cell mixture

Adult hair follicle

Embryonic skin

Fig. 6.2 The method used to reproduce the bioengineered hair follicle germ relied on reproducing
the epithelial-mesenchymal interactions of the natural hair follicle. (a) Replacement of hair
follicle- inductive mesenchymal cell in afollicular skin or hair follicle via the implantation of hair
follicle-derived mesenchymal cells. (b) De novo skin regeneration method via the engraftment of
cell aggregates. (c) Orthotopic hair follicle regeneration by intracutaneous transplantation of the
bioengineered hair follicle germ reconstituted using the organ germ method

K.-e. Toyoshima and T. Tsuji