Organ Regeneration Based on Developmental Biology

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Furthermore, an attractive concept for generating a bioengineered tooth unit
composed of a mature tooth, PDL and alveolar bone through in vivo transplantation
into the subrenal capsule has been developed (Fig. 5.4b). Multiple bioengineered
tooth units surrounded by alveolar bone could also be generated through transplant-
ing several tooth germs in a size-control device (Oshima et al. 2011 ). Each bioengi-
neered tooth had the correct tooth structure including the pulp cavities and the

Cell injection into collagen gel

Scale bar:400μm

A)

Scale bar: 500μm Scale bar: 50μm

D

AB

PDL

E D

Single bioengineered tooth unit

Photograph Micro CT

B)

HE staining (incisor, molar)

Scale bar : 200 μm

Multiple bioengineered tooth units

Photograph Micro CT

Scale bar : 200 μm

Bioengineered tooth unit

HE staining

3D-cell manipulation by an organ germ method

E

M

Scale bar:500 mm

Fig. 5.4 The organ germ method: a novel three-dimensional cell-processing system. (a) Tooth
germ-derived mesenchymal cells at a high density are injected into the centre of a collagen drop.
Subsequently, tooth germ-derived epithelial cells are injected into the drop adjacent to the mesen-
chymal cell aggregate. Within 1 day of organ culture, the formation of bioengineered tooth germ
with the appropriate compartmentalisation between the epithelial and mesenchymal cells and cell-
to- cell compaction was observed (left panels). Bioengineered incisor and molar tooth germs,
which were reconstituted using dissociated cells isolated from respective tooth germs, developed
in organ culture over 14 days (right panels). (b) Transplantation of this bioengineered tooth germ
into a subrenal capsule for 30 days (left-upper panels). Multiple bioengineered tooth units sur-
rounded by alveolar bone can be generated by transplanting several tooth germs (left-lower pan-
els). A bioengineered tooth unit comprising a mature tooth, periodontal ligament and alveolar bone
with the correct tooth-tissue structure such as the enamel (E), the dentin (D), the periodontal liga-
ment (PDL) and the alveolar bone (right panels)

M. Oshima and T. Tsuji