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.