Understanding the functional characteristics and cellular tropism of SARS-CoV-2, and the pathogenesis that leads to multi-organ failure and death has prompted an unprecedented adoption of organoid models. Successful drug discovery and vaccine development rely on preclinical models that faithfully recapitulate the viral life cycle and the host cell response to infection. Human stem cell-derived organoids fulfil these criteria. In the recent review article published by MDPI, Tran et al. highlighted the role of organoids in the study of SARS-CoV-2 infection and modelling of COVID-19 pathogenesis.

Dolly the reporter from LAB-A-PORTER has extracted several highlights from the MDPI review article while we selected and sourced research use only (RUO) products for your next organoid culture research projects.

Highlights from MDPI (1) : The role of organoid models on SARS-CoV-2 research

  • In vitro models for SARS-COV-2 infection are essential for the understanding of host and viral factors supporting the cell tropism and the viral replication cycle.
      • They are needed for preparing the viral inoculum for further research and pre-clinical evaluations of medical countermeasures against COVID-19.
  • Serious limitations of classical cell lines
      • They are not human or are derived from human cancers
      • Do not faithfully replicate healthy human physiology.
  • Organoids can reproduce the pathology of COVID-19 in their specific tissue of origin.
      • They have been rapidly adopted during COVID-19.

Highlights from MDPI (2) : Diverse human organoids employed in SARS-CoV-2 research

Respiratory tract organoids

  • Researchers investigate the regions and cell types of the respiratory tract that can be potentially infected with SARS-CoV-2.
  • Examples of organoid models employed: Human airway epithelium (HAE) organoids, respiratory and more complex organoid models on a chip, human ES cell-derived lung organoids (hESC-LO) and the alveolar-like organoids

Intestine epithelium organoids

  • Researchers investigate the potential for an oral-fecal route of transmission of this virus.
  • Examples of organoid models employed: human small intestinal organoids (hSIOs)

Liver organoids

  • The susceptibility of a liver cancer cell line, Huh7 cells, to SARS-CoV-2 infection in vitro and other clinical factors prompted researchers to further analysis and its infection potential.
  • Examples of organoid models employed: human liver organoids, bipotent ductal organoids, non-alcoholic steatohepatitis (NASH) patient-derived organoids

Brain organoids

  • Researchers investigate the potential of SARS-CoV-2 infection in the brain and identify target cell types in the brain.
  • Examples of organoid models employed: human brain organoids, pure choroid plexus organoids

Kidney organoids

  • Researchers investigate the potential of infection of kidney cells by SARS-CoV-2.
  • Examples of organoid models employed: hES-derived kidney epithelium organoids, kidney epithelium organoids

The eye organoids

  • Researchers investigate if ocular surfaces susceptible to SARS-CoV-2 infection.
  • The culture was established from cells isolated from eye regions of healthy donors and infected with SARS-CoV-2.
  • Examples of organoid models employed: Human ES cell and iPS cell-derived retinal, ‘whole eye’ organoids

    Vasculature organoids

    • The vasculature, like neuronal networks, is of great importance to our understanding of COVID-19 pathogenesis as it encompasses all organs.
    • The endothelium lines the inner surface of all blood vessels and plays crucial roles in human physiology and pathophysiology.
    • The endothelium functions in both adaptive and innate immunity.
    • Examples of the organoid model employed: hiPS-derived capillary organoids, hiPS-derived kidney organoids (which contain multiple renal cell types and structures, as well as the vasculature)

    Highlights from MDPI (3) : What have we learned from organoid-based SARS-CoV-2 research?

    1. Limitations of drug screens on conventional cell lines

     

    • Viral infection cannot induce an IFN-I response in classical cell lines.
        • Any effect of drugs and neutralizing antibodies may not translate to humans.
    • Classical cell lines, such as Vero cells, are not human but monkey kidney-derived.
        • May not predict toxicity to human cells

      2. Clinical isolates and viral stocks

       

      • SARS-CoV-2 stocks prepared in Vero cells can harbour mutations in or deletions of the multibasic cleavage site (MBCS), affecting the ability of the virus to infect human airway cells and viral transmission from infected to uninfected animals in the experiment.

      3. Accurate pre-clinical models of SARS-CoV-2 transmission and respiratory disease

       

      • Air-liquid interface human nasal epithelial (ALI-HNE) and matrix-embedded human nasal epithelial (HNE) organoids are proving to be excellent research models of SARS-CoV-2 variant transmissibility.
      • The primary human respiratory organoids established from different regions of the respiratory tract offer insights into viral transmissibility and pathogenicity of SARS-CoV-2 variant as they emerge and the potential for immune evasion.

      Selected compositions for organoid culture recipe by LAB-A-PORTER

      LUNG ORGANOID
      Proteins & Growth Factors
      Small Molecules
      3D Growth Matrix
      References

      Dye B.R. et al. (2015) eLIFE. 4:e05098

      KIDNEY ORGANOIDS
      Proteins & Growth Factors
      Small Molecules
      3D Growth Matrix
      References

      Xia Y. et al. (2014) Nature Protocols. 9:2693.
      Xia Y. et al. (2013) Nature Cell Biology. 15:1507.
      Takasato M. et al. (2014) Nat. Cell Biol. 16:118

      INNER EAR ORGANOIDS
      Proteins & Growth Factors
      Small Molecules
      3D Growth Matrix
      References

      Koehler K.R. and E. Hashino (2014) Nat. Protocols. 9:1229.

      LIVER ORGANOID
      Proteins & Growth Factors
      Small Molecules
      3D Growth Matrix
      References

      Mahe M. et al. (2013) Curr. Protoc. Mouse Biol. 3:217
      Sato T. and H. Clevers (2015) Cell. 161:1700
      Bartfeld S. et al. (2015) Gastroenterology. 148:126

      PANCREATIC ORGANOID
      Proteins & Growth Factors
      Small Molecules
      3D Growth Matrix
      References

      Sato T. and H. Clevers (2015) Cell. 161:1700
      Boj S.F. et al. (2015) Cell. 160:324.
      Broutier L. et al. (2016) Nature Protocols. 11:1724

      PROSTATE ORGANOID
      Proteins & Growth Factors
      Small Molecules
      3D Growth Matrix
      References

      Karthaus W.R. et al. (2014) Cell. 159:163.
      Drost J. et al (2016) Nat. Protocols. 11:347

      SMALL INTESTINAL AND COLONIC ORGANOIDS
      Proteins & Growth Factors
      Small Molecules
      3D Growth Matrix
      References

      Mahe M. et al. (2013) Curr. Protoc. Mouse Biol. 3:217
      Sato T. et al. (2011) Gastroenterology. 141:1762
      Sato T. and H. Clevers (2015) Cell. 161:1700
      Sato T. and H. Clevers (2009) Nature. 459:262
      Jung P. et al. (2011) Nature Medicine. 17:1225

      BRAIN ORGANOIDS
      Proteins & Growth Factors
      Small Molecules
      3D Growth Matrix
      References

      Lancaster M.A. and J. A. Knoblich (2014) Nat. Protocols.
      9:2329
      Mariani J. et al. (2015) Cell. 162:375
      Li Y. et al. (2017) Cell Stem Cell 20:1

      RETINA ORGANOIDS
      Proteins & Growth Factors
      Small Molecules
      3D Growth Matrix
      References

      Nakano T. et al. (2012) Cell stem cell. 10: 771

      STOMACH ORGANOIDS
      Proteins & Growth Factors
      Small Molecules
      3D Growth Matrix
      References

      Mahe M. et al. (2013) Curr. Protoc. Mouse Biol. 3:217
      Sato T. and H. Clevers (2015) Cell. 161:1700
      Bartfeld S. et al. (2015) Gastroenterology. 148:126

      IMMUNO GERMINAL CENTER-LIKE ORGANOIDS
      Proteins & Growth Factors
      3D Growth Matrix
      References

      Purwada A. and Singh A. (2017) Nat. Protocols. 12:168

      MAMMARY ORGANOIDS
      Proteins & Growth Factors
      Small Molecules
      3D Growth Matrix
      References

      Jardé T.et al. (2016) Nat. Commun. 7: 13207
      Jamieson PR. et al. (2016) Develompent. :dev-145045

      Biogems, theWell Bioscience and Peprotech products are for research use only (RUO) and are NOT FOR THERAPEUTIC OR DIAGNOSTIC USE. 

       References:

      1. Tran, Bang M., et al. “Organoid Models of SARS-CoV-2 Infection: What Have We Learned about COVID-19?” Organoids, vol. 1, no. 1, Mar. 2022, pp. 2–27. Crossref, https://doi.org/10.3390/organoids1010002.

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