Organoids – the past, present and the future

Organoid models are known for their thrilling opportunities and potential for scientists in studying developmental processes, drug testing and disease modelling, including genetic, developmental disorder, degenerative disorders, and cancer.

Past

  • The earliest 3D organoid models were first reported over 40 years ago [1].
  • Early organoid models demanded large numbers of starting cells; they were not able to use for high-throughput screening, and often demonstrated limited in vitro viability [1].
  • The advancement in multipotent stem and progenitor cell isolation has gotten rid of the disadvantages of early organoid models and has granted researchers to work out highly reproducible, long-lived organoids [1].

Present

  • Nowadays, organoids allow valuable disease modelling when adequate animal models are not available;
  • They can be used for more efficient testing of drug efficacy and toxicity by eliminating discrepancies due to the differences between animal and human cells [1];
  • They might also serve as a tool for drug testing which could potentially decrease the use of animals for pre-clinical trials [1].

Future

  • The hope for scientists is that organoids are another step in the long journey towards in vitro construction of tissues and organs for transplantation into patients [1].

As of 2020, there are 17 reported human organoid systems by tissue of origin to date, including the brain, optic cup/retina, salivary gland, thyroid, lung, blood vessel mammary gland, liver, kidney, pancreas, stomach, intestine, fallopian tube, endometrium, bladder, and prostate [2].

Quick review series about organoids

In the upcoming weeks, we are going to discuss the development of organoid technology in scientific research by different organoid systems. In this week, we are going to have a quick review on pancreatic organoids.

The Pancreatic Organoids

  • The rise of pancreatic organoids
  • Challenges on current pancreatic research
  • Opportunities on pancreatic organoids
  • Current usage of pancreatic organoids
  • The future – a more mature islet organoid development
  • Our selected composition for pancreatic organoid culture

The rise of pancreatic organoids

  • Deadliest pancreatic malignancy, diabetes, process, and cellular response of pancreas during viral infection are only a few examples of unsolved pancreatic mysteries for scientists.
  • Before the rise of organoids, scientists have put a lot of effort to model the biology of human organs by utilizing the differentiation of human stem cells in 2D, bioprinting of human cells and culture of cells in the microfluidic device, to name but a few [2].
  • In 2015, the establishment of patient-derived adult stem cell-based pancreatic tumour organoids was first reported [7].

Challenges

  • Studies on diabetes have long been restricted by a lack of reliable disease models [8].
  • Research indicates that earlier detection of pancreatic tumours could quadruple survival rates, however, no validated and reliable tests for early detection of pancreatic cancer currently exist [6].

Opportunities

  • The development of pancreatic organoids makes research on diabetes easier and earlier detection of pancreatic cancers possible.
  • It can be used in the field of personalized medicine, like in the areas of pancreatic tissue pathology, drug development and the assessment of biomarkers for diagnosis.

The future - a more mature islet organoid development

  • Currently, established islet organoids are generally immature when compared with indigenous islets [8].
  • A perfect islet organoid should summarize the characteristic of islet development and the function of mature islets under both physiological and pathological conditions [8].
  • To enhance the efficiency of current islet organoids, a comprehensive study on islet development is essential. In combining interdisciplinary methods, such as 3D scaffolds or bioprinting, a more appropriate physiological niche for islet organoids can be developed [8].

    Selected compositions for pancreatic organoid culture by Lab-A-Porter

    EGF

    EGF is a potent growth factor that stimulates the proliferation of various epidermal and epithelial cells. It has been shown to inhibit gastric secretion and be involved in wound healing.

    Noggin

    Noggin belongs to a group of diffusible proteins that bind to ligands of the TGF-β family and regulate their activity by inhibiting their access to signalling receptors.                                                        

    FGF-10

    FGF-10 is a heparin-binding growth factor that belongs to the FGF family. Proteins of this family play a central role during prenatal development, postnatal growth and regeneration of a variety of tissues.

    R-Spondin-1

    R-Spondin-1 is expressed in certain areas of the developing central nervous system, as well as in the adrenal glands, ovary, testis, thyroid, and trachea.                                                            

    Wnt-3a

    Wnt-3a signalling is essential for various morphogenetic events, including embryonic patterning, cell determination, cell proliferation, CNS development, and cytoskeletal formation.           

    A-83-01

    A 83-01 is a potent activin receptor-like kinase inhibitor and is reported to inhibit Smad signalling and epithelial-to-mesenchymal transition by transforming growth factor-beta.                                                 

    Nicotinamide

    Nicotinamide is an amide of nicotinic acid, a vitamin of the B complex. In cells, it is incorporated into NADP+ and NAD+, coenzymes for a wide variety of enzymatic oxidation-reduction reactions.

    Gastrin

    Gastrin is a peptide hormone that is a major physiological regulator of gastric acid section and a promoter of gastric mucosal growth.                                                                                                                                         

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    [Poster] Reagents for Organoid Research

    [Brochure] Organoids - Mini organ in a dish

    [Brochure] Building Blocks for Organoid Research

    References:

    1. “Organoids.” Organoids Brochure: Research & Products, Peprotech, 2021, https://www.peprotech.com/en/organoids-brochure-research-products.
    2. Kim, Jihoon et al. “Human organoids: model systems for human biology and medicine.” Nature reviews. Molecular cell biology vol. 21,10 (2020): 571-584. doi:10.1038/s41580-020-0259-3
    3. Gonçalves, Carla A et al. “A 3D system to model human pancreas development and its reference single-cell transcriptome atlas identify signalling pathways required for progenitor expansion.” Nature communications vol. 12,1 3144. 25 May. 2021, doi:10.1038/s41467-021-23295-6
    4. Yao, Jia et al. “A pancreas tumour derived organoid study: from drug screen to precision medicine.” Cancer cell international vol. 21,1 398. 27 Jul. 2021, doi:10.1186/s12935-021-02044-1
    5. Huang, Ling et al. “Commitment and oncogene-induced plasticity of human stem cell-derived pancreatic acinar and ductal organoids.” Cell stem cell vol. 28,6 (2021): 1090-1104.e6. doi:10.1016/j.stem.2021.03.022
    6. Henderson, Emily. Researchers Develop First 3D Organoid Models of the Pancreas from Human Stem Cells. News Medical, 28 Apr. 2021, Researchers develop first 3D organoid models of the pancreas from human stem cells.
    7. Driehuis, Else et al. “Establishment of Pancreatic Organoids from Normal Tissue and Tumors.” STAR protocols vol. 1,3 100192. 4 Dec. 2020, doi:10.1016/j.xpro.2020.100192
    8. Zhang, Xiaofei et al. “Islet organoid as a promising model for diabetes.” Protein & cell, 1–19. 10 Mar. 2021, doi:10.1007/s13238-021-00831-0
    9. Kimura-Nakajima, Chiemi et al. “Ngn3-Positive Cells Arise from Pancreatic Duct Cells.” International journal of molecular sciences vol. 22,16 8548. 9 Aug. 2021, doi:10.3390/ijms22168548
    10. Sándor, Gyöngyvér Orsolya et al. “Wnt Activity and Cell Proliferation Are Coupled to Extracellular Vesicle Release in Multiple Organoid Models.” Frontiers in cell and developmental biology vol. 9 670825. 24 Jun. 2021, doi:10.3389/fcell.2021.670825
    11. Studies Using ‘Model’ Organs Show How SARS-CoV-2 Can Infect Wide Range of Cell Types and Even Change Function of Cells, Including the Insulin-Producing Cells of Pancreas. American Association for the Advancement of Science, 29 Sept. 2021, https://www.eurekalert.org/news-releases/929656.

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