Abstract
Many treatments have been used for glucose metabolism diseases such as type 2 diabetes, and all of those treatments have several advantages as well as limitations. This review introduces a 3D co-culture intestinal organoid system developed from stem cells, which has the special function of simulating human tissues. Recent studies have revealed that the gut is an important site for exploring the interactions among glucose metabolism, gut microbial metabolism, and gut microbiota. Therefore, 3D intestinal organoid systems can be used to imitate the congenital errors of human gut development, drug screening, food transportation and toxicity analysis. The intestinal organoid system construction methods and their progress as compared with traditional 2D culture methods have also been summarised in the manuscript. This paper discusses the research progress in terms of intestinal organoids applicable to glucose metabolism and provides new ideas for developing anti-diabetic drugs with high efficiency and low toxicity.
| Original language | English |
|---|---|
| Article number | 100402 |
| Journal | Current Research in Food Science |
| Volume | 6 |
| DOIs | |
| Publication status | Published - Jan 2023 |
Bibliographical note
Publisher Copyright:© 2022 The Authors
Funding
This work was supported by Key Project of the Natural Science Foundation of Fujian Province ( 2020J02032 ) and Fujian ‘Young Eagle Program’ Youth Top Talent Program . Organoid establishment and differentiation depend on multiple growth factors. R-spondin1, EGF, and noggin are three essential growth factors in the medium. Among them, R-spondin1, an essential Wnt signalling enhancer and Lgr5 ligand, leads to the massive proliferation of crypts in vitro (KIM et al., 2005). EGF signalling mainly promotes the proliferation of intestinal stem cells (Spit et al., 2018). Noggin, a bone morphogenetic protein pathway inhibitor, hinders the proliferation of stem cells and increases the crypt number in organoids (Lanik et al., 2018). Additionally, the choice of ECM is also a key factor that affects the development of organoids (Lanik et al., 2018). Therefore, as a basement membrane to support the growth of intestinal crypts, Matrigel is the most important material for culturing organoids. However, Matrigel may vary significantly from batch to batch, and it is difficult to guarantee that each batch will have the same number of growth factors and other vital components (Yin et al., 2019c). Furthermore, Matrigel has certain safety concerns for clinical use, especially in terms of its ability to control biochemical and biophysical properties, as well as the possibility of pathogen transfer and the tissue-specific signals essential for organoid development and maturation (Capeling et al., 2019). The use of decellularised small intestine-derived hydrogel instead of Matrigel maximises the recapitulation of the gut's inherent ECM microenvironment to support the growth and development of intestinal organoids, reaching a level comparable to that of Matrigel. Giobbe et al. (2019) built decellularised tissue-derived ECM hydrogels using decellularised porcine small intestine (SI) mucosa/submucosa. These ECM gels can be employed for mouse and human organoid cultures, organoid administration in vivo, and cell growth with stable transcriptome signatures. Capeling et al. (2019) used non-adhesive alginate hydrogels as a substitute for Matrigel to culture HIOs differentiated from human PSCs. In this study, alginate-grown and Matrigel-grown HIOs were hardly distinguishable, and both were similar to human foetal intestine. Moreover, non-adhesive alginate hydrogels overcome many of the limitations of Matrigel and are more cost-effective than Matrigel or polyethylene glycol (Kim et al., 2022).This work was supported by Key Project of the Natural Science Foundation of Fujian Province (2020J02032) and Fujian ‘Young Eagle Program’ Youth Top Talent Program.
| Funders | Funder number |
|---|---|
| Fujian ‘Young Eagle Program’ Youth Top Talent Program | |
| European Genetics Foundation | |
| Natural Science Foundation of Fujian Province | 2020J02032 |
Keywords
- 3D co-culture
- Glucose metabolism
- Intestinal organoid
