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  1. Home
  2. Acquired Genetic Changes In Human Pluripotent Stem Cells: Origins And Consequences.
  1. Home
  2. Acquired Genetic Changes In Human Pluripotent Stem Cells: Origins And Consequences.

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Acquired genetic changes in human pluripotent stem cells: origins and consequences.

Jason Halliwell1, Ivana Barbaric2, Peter W Andrews3

  • 1Centre for Stem Cell Biology, Department of Biomedical Science, The University of Sheffield, Sheffield, UK.

Nature Reviews. Molecular Cell Biology
|September 24, 2020

View abstract on PubMed

Summary
This summary is machine-generated.

Pluripotent stem cells (PSCs) can acquire genetic mutations during long-term culture, raising safety concerns for regenerative medicine. These rare, advantageous mutations arise because PSCs are programmed to die when facing genomic damage.

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Area of Science:

  • Stem cell biology
  • Genetics
  • Regenerative medicine

Background:

  • Human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), are vital for regenerative medicine.
  • Long-term culture of hPSCs can lead to the accumulation of genetic alterations, such as chromosomal abnormalities and mutations in cancer-associated genes (e.g., TP53).
  • These acquired genetic changes pose significant safety risks for hPSC-derived cell therapies.

Purpose of the Study:

  • To review the types of genetic mutations acquired by human pluripotent stem cells (PSCs).
  • To discuss the mechanisms underlying the accumulation of these mutations.
  • To address the safety implications of PSC genetic instability for regenerative medicine.

Main Methods:

  • Review of existing literature on genetic alterations in human pluripotent stem cells (PSCs).
  • Analysis of mutation types, including chromosomal gains/losses and gene mutations (e.g., TP53).
  • Discussion of mechanisms driving mutation acquisition and selection in PSCs.
  • Main Results:

    • Human PSCs commonly acquire genetic changes like chromosomal aberrations and mutations in cancer-associated genes during prolonged culture.
    • Despite a low underlying mutation rate, PSCs exhibit susceptibility to genomic damage.
    • PSC genetic variants often confer a selective growth advantage, leading to their prevalence despite being rare events.

    Conclusions:

    • Genetic instability in PSCs is a critical concern for the clinical application of cell therapies.
    • Understanding the mechanisms of PSC mutation accumulation is essential for developing safer cell-based regenerative treatments.
    • Current detection methods may fail to identify low-frequency mutations, necessitating improved monitoring strategies.