4. Applications
4.1 Disease modeling
The lack of suitable in-vitro models to accurately simulate
specific tissues and disease states is an important factor restricting
basic research and translational research. Organoids reproduce certain
characteristics of tissues and organs, opening the door to a new world
for disease research and drug development. As we all know, radiotherapy
is a common method for cancer treatment, but there are many
complications. In patients with head and neck cancer, radiation cause
oral mucositis, which leads to loss of taste[74,75]. Radiation was
given to taste bud organoids to construct a disease model of oral
mucositis, and it was verified by a mouse experiment. The research
showed that the results of organoids are consistent with that of the
mouse test, that is, the SIRT1 inhibitor nicotinamide significantly
relieved oral mucositis[12]. In previous clinical trials conducted
in 2016, it was found that BIA 10-2474 (a fatty acid amide hydrolase
inhibitor with the potential to treat a variety of neurological
diseases) would produce neurotoxic accumulation in humans, but this
situation did not occur in experimental animals. ChP organoids derived
from human iPSCs also exhibit the toxicity accumulation of BIA 10-2474,
indicating that this organoid model is more suitable for toxicity
testing of new therapies than experimental animals[76].
Compared with the two-dimensional culture system, organoids help clarify
the development, homeostasis, and pathogenesis of diseases and provide
possible new approaches for the diagnosis and treatment of diseases.
This organoid model was grown in a micro-machined chamber and was used
for long-term in-situ imaging. It has been used to simulate cortical
folding and study the pathogenesis of encephalopathy[77]. Studies
have shown that brain organoids prepared from induced pluripotent stem
cells of patients with lissencephaly have mitotic defects in the outer
radial glial cells, which are rarely seen in mouse models[78]. Brain
organoids are also used to study the Zika virus, which preferentially
infects neural progenitor cells and reduces their proliferation and
viability. This may be an important reason for the Zika virus to cause
head deformities[79]. Talking about neural/stem cell biology,
organoids could better track neurons and establish more predictivein-vitro disease models[80]. In regenerative medicine,
artificial tissue cultivating was used to establish pathological
mechanism research and transplantation research models[81].
Scientists combined with 3D culture organoid technology to develop a
type 2 alveolar cell organoid model that could be cultured for a long
time without a trophoblast for the development of vaccines and
therapies[82]. Then, 3D self-rolled biosensor arrays (3D-SR-BAs) of
either active field-effect transistors or passive microelectrodes were
implemented to interface human cardiac spheroids in 3D which enabled the
development of organ-on-an-electronic-chip (organ-on-e-chip)
platform[83] (Figure 5a-b). For taste sensing, bio-artificial tongue
devices have been reported to sense comprehensive taste[9]. This is
not only a device for taste detection but also provides an effective
sensing device to simulate the function of the tongue outside the body,
thereby providing a practical basis for exploring the mechanism of
taste.