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Regenerative Medicine

Genomic instability in cultured stem cells: associated risks and underlying mechanisms

    Andrew L Ross

    Interdisciplinary Stem Cell Institute, University of Miami, Miller School of Medicine, Miami FL 33136, USA; Department of Dermatology, Melanoma Program Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Room 912, BRB, 1501 NW 10th Ave, Miami, FL 33136, USA.

    Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA

    ,
    Daniel E Leder

    Interdisciplinary Stem Cell Institute, University of Miami, Miller School of Medicine, Miami FL 33136, USA; Department of Dermatology, Melanoma Program Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Room 912, BRB, 1501 NW 10th Ave, Miami, FL 33136, USA.

    Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA

    ,
    Jonathan Weiss

    Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA

    ,
    Jan Izakovic

    Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA

    &
    James M Grichnik

    † Author for correspondence

    Interdisciplinary Stem Cell Institute, University of Miami, Miller School of Medicine, Miami FL 33136, USA; Department of Dermatology, Melanoma Program Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Room 912, BRB, 1501 NW 10th Ave, Miami, FL 33136, USA.

    Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA

    Published Online:https://doi.org/10.2217/rme.11.44

    Embryonic stem cells, mesenchymal stem cells and induced pluripotent stem cells expanded in vitro exhibit genomic instability. Commonly reported abnormalities include aneuploidy, deletions and duplications (including regions also amplified in cancer). Genomic instability confers an increased risk of malignant transformation that may impact the safety of cultured stem cell transplantation. Possible mechanisms responsible for this genomic instability include DNA repair mechanism abnormalities, telomere crisis, mitotic spindle abnormalities and inappropriate induction of meiotic pathways. Prior to widespread use of these cells in regenerative medicine, it will be critical to gain an understanding of the mechanisms responsible for genomic instability to develop strategies to prevent the accrual of chromosomal defects during expansion in vitro.

    Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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