1. Introduction
Taste buds are specialized organ for taste sensation, which are able to
detect and report oral irritation caused by chemicals such as alcohol
and capsaicin, thereby avoiding the intake of toxic and harmful foods.
With the in-depth study of the coronavirus disease 2019 (COVID-19), in
addition to common symptoms such as fever, cough, dyspnea, fatigue, and
myalgia, loss of smell and taste are gradually being taken into
consideration. A new study showed that up to 41% of people infected
with severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2) have
a loss of taste[1]. At the same time, dysgeusia is very common in
patients with head and neck cancer, and as many as 75% of patients
complain of loss of taste[2]. Nearly 60% of patients receiving
systemic chemotherapy will report a certain degree of dysgeusia, which
is related to the type of cytotoxic drugs and the presence of oral
mucositis[3]. A mount of factors such as cancer treatments,
bacterial and viral illness, age and other medications may damage the
taste system and reduce its function[4,5].
Although tricyclic antidepressants[6], clonazepam or diazepam[7]
have been proved to be useful for improving the abnormal sensation of
taste, it’s still lack effective treatment interventions. Most research
on taste has focused at the cellular level, revealing the expression of
receptors and the transmission of signals[8-10]. Meanwhile, since
most of the mechanisms that cause dysgeusia are unclear, there is no
clear treatment plan for dysgeusia.
Therefore, in 2018, scientists made suggestions at a conference that
potential therapies for dysgeusia could be provided by various
approaches such as stem cell therapies, gene therapies, clinical
research and patient engagement [11]. On the other hand, with the
continuous deepening of research, animal models are gradually unable to
meet the requirements of the experiment. For example, the immune
rejection problem caused by organ transplantation, or the inconsistent
test results caused by the difference between animal and human cells,
and the test of drug efficacy and toxicity couldn’t get more effective
and true results. Copying and reconstructing human organs has become one
of the directions that scientists focus on. Researchers have built taste
bud organoids derived from the oral mucositis model mice to study the
therapeutic effects of drugs on taste loss[12]. It is a model based
on a 3D in-vitro cell culture system that is highly similar to
the source tissues or organs in the body and widely used in cancer
research[13]. Compared with cells, organoids have shown great
advantages in many examples such as the earliest intestinal
organoids[14], primary intestinal organoids in patients with cystic
fibrosis[15], human pancreatic cancer organoids[16], liver
cancer organoids[17], breast cancer organoids[18], and
colorectal cancer organoids[19]. These tumor organoids show the same
phenotype and disease characteristics as the original tumor tissues.
They are used as models to study tumor occurrence and development,
personalized medicine and new anti-tumor drug screening. Besides,
organoids are also derived from normal tissues to study developmental
problems and the mechanism of occurrence and development of
diseases[20-23]. Within this context, there are relatively few
studies focusing on taste bud organoids. However, significant progress
and some interesting results have been achieved in the fields of taste
bud organoids, which have attracted more and more attention. Therefore,
through the establishment of taste bud organoids, taste transduction
mechanisms or dysgeusia are capable of being studied more efficiently,
which aims to achieve the purpose of restoring taste.
Animals must undergo the activation of TRP channels during the process
of obtaining nutrients through food, so as to meet the needs of
metabolism and growth and development. For example, TRPV1 gene
have been associated with alterations in salty taste sensitivity and
salt preference[24]. TRPV4 contributes to sour taste
sensing[25]. TRPM5 has the ability to perceive bitterness, sweetness
and umami[26,27]. Meanwhile, missing function of TRP channels have
been associated with reduced ability to detect taste
stimuli[25,27,28]. Bitter taste is regulated by 30 TAS2R bitter
taste receptor genes[29]. The perception of sweetness and umami is
realized by forming heteromers between TAS1R2 and TAS1R1 and TAS1R3,
respectively[30]. Furthermore, Dias and colleagues found different
genotypes and temperature have significant differences in sensitivity
and preference to salty and sweetness taste[31,32]. Another study
revealed the genetic basis of variation in taste perception between two
populations with different lifestyle. The results showed there is a
strong divergence in genes and transduction pathways of taste signals
between two groups with different lifestyle[33]. Genes carry the
genetic information of species, and the study of genes can fundamentally
reveal the mechanism of diseases and promote the development of
medicine. Therefore, using taste bud organoids to study taste
preferences related genes can promote the development of this process
faster.
This review gives a systemic and comprehensive introduction to the
preparation and application of taste bud organoids towards chemical
sensing mechanisms. For the first, the basic structure and function of
taste buds will be brief introduced based on taste transduction
pathways, i.e. the pathway of ion channels and G protein-coupled
receptors (GPCR). Then two main types of taste receptors are introduced,
i.e. T1Rs and T2Rs, which can identify taste molecules and transmit
taste signals downstream individually or at dimers manner. At the same
time, taste receptors are not only functioned in taste buds but also
play roles in the intestines, airways, and brain. Therefore, in addition
to sensing taste, taste receptors can also cause an immune response in
the body to deal with inflammation. Most importantly, the appearance of
taste organoids provides a very convenient tool for the study of taste
functions. Drawing lessons from other 3D structures to replicate certain
characteristics of tissues and organs, and to simulate the application
of disease states, taste bud organoids can also be used in the fields of
drug screening, toxicity detection, disease modeling, and regenerative
medicine in the future, with broad development prospects. For the next,
this review also summarizes the approaches for preparation of taste bud
organoids from stem/ progenitor cells or tissue. These approaches
provide a very valuable reference for the study of taste bud organoids,
allowing more scientists to conduct more in-depth research on taste
sensation. Then, the applications of other types of organoids in
diseases and biosensors are summarized and discussed. This is also the
direction of the future development of taste bud organoids. Finally, the
limitations and challenges of the development of taste bud organoids are
discussed, and future development trends have also been prospected.