Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Stem cells

Stem cell-derived organoid models: defying the Hayflick limit

Nature Reviews Genetics (2023)Cite this article

Subjects

In the mid-twentieth century, our ability to expand non-transformed, genetically stable, diploid cells, was considered impossible. This dogma arose from the studies by Hayflick and Moorhead in 1961, who aimed to achieve a culture model that would retain normal ploidy to be used as a cell source to study human biological processes or to produce vaccines. However, Hayflick’s observations indicated that diploid epithelial cells could not be propagated in culture for longer than five sub-cultivations; only fibroblasts and tumour cells could be expanded. From these findings, Hayflick postulated the dogma that there was a limit for the propagation of primary epithelial cells while retaining normal ploidy. This theory, according to which only cancer cells with aberrant ploidy and unstable genomes would be expandable in culture, became known as the Hayflick limit. The Hayflick limit represented a significant limitation in the study of human biology as well as for some therapeutic applications, in particular the vaccine production Hayflick was aiming for. This dogma persisted for the remainder of the century until the advent of organoid cultures, at the end of the first decade of the twenty-first century.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

References

Original article

  • Hayflick, L. & Moorhead, P. S. The serial cultivation of human diploid cell strains. Exp. Cell Res. 25, 585–621 (1961)

    Article  CAS  Google Scholar 

Related article

  • Sato, T. et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459, 262–265 (2009)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Max Planck Institute of Molecular Cell Biology and Genetics, Center for Systems Biology Dresden and Cluster of Excellence Physics of Life, TU Dresden, Dresden, Germany

    Meritxell Huch

Authors
  1. Meritxell Huch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Meritxell Huch.

Ethics declarations

Competing interests

M.H. is listed as co-inventor on several patents related to organoid technology.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Huch, M. Stem cell-derived organoid models: defying the Hayflick limit. Nat Rev Genet (2023). https://doi.org/10.1038/s41576-023-00577-x

Download citation

  • Published:

  • DOI: https://doi.org/10.1038/s41576-023-00577-x

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing