2020
DOI: 10.1016/j.bbadis.2019.03.017
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DNA repair fidelity in stem cell maintenance, health, and disease

Abstract: Stem cells are a sub population of cell types that form the foundation of our body, and have the potential to replicate, replenish and repair limitlessly to maintain the tissue and organ homeostasis. Increased lifetime and frequent replication set them vulnerable for both exogenous and endogenous agents-induced DNA damage compared to normal cells. To counter these damages and preserve genetic information, stem cells have evolved with various DNA damage response and repair mechanisms. Furthermore, upon experien… Show more

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Cited by 35 publications
(33 citation statements)
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References 165 publications
(167 reference statements)
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“…In vitro expansion reduces replicative potential and multipotency; it drives senescence; it reduces DNA polymerase and DNA repair efficiencies, thus leading to DNA damage accumulation, such as cytogenetic alterations (deletions, duplications, rearrangements), mutations, epigenetic changes [52,53,54,55,56,57,58,59]. This applies also to stem cells [60] (for a review on stem cell DNA damage and aging see Behrens et al [61]). There are two possible outcomes of DNA damage: erroneous repair and persistent DNA damage; the first can lead to transformation, the second can block transcription and replication driving the aging process [62].…”
Section: The Safety Issuementioning
confidence: 99%
See 1 more Smart Citation
“…In vitro expansion reduces replicative potential and multipotency; it drives senescence; it reduces DNA polymerase and DNA repair efficiencies, thus leading to DNA damage accumulation, such as cytogenetic alterations (deletions, duplications, rearrangements), mutations, epigenetic changes [52,53,54,55,56,57,58,59]. This applies also to stem cells [60] (for a review on stem cell DNA damage and aging see Behrens et al [61]). There are two possible outcomes of DNA damage: erroneous repair and persistent DNA damage; the first can lead to transformation, the second can block transcription and replication driving the aging process [62].…”
Section: The Safety Issuementioning
confidence: 99%
“…MSC aging is accompanied by a series of genetic, epigenetic, transcriptional and translational changes affecting cell function [60,69] and is a critical aspect to be considered for cellular therapy and safety assessments [70]. Both in vivo [61] and in vitro aging should be considered.…”
Section: Senescencementioning
confidence: 99%
“…In brief, four possible mechanisms have been described by which progenitor and stem cells respond to an excess of irreversible DNA damage, and in the context of regeneration they could also be applied to the other cell populations of the blastema. These mechanisms are senescence, apoptosis, differentiation, and cancer 51,54 (see Figure 2).…”
Section: The Fate Of Damaged Blastema Cellsmentioning
confidence: 99%
“…As for other cellular types, aging of MSCs is a dynamic process taking place through a series of steps that follow the initial growth decline [31,57]. It is accompanied by functional alterations due to metabolic, genetic, epigenetic, transcriptional and translational changes [31,[58][59][60] (Figure 1). Senescent MSCs loose metabolic flexibility, they show an impairment of the autophagic flux with reduced active vacuoles, and an impairment of the ubiquitin-proteasome pathway, the main proteolytic cellular system to degrade damaged proteins [39].…”
Section: Msc Senescencementioning
confidence: 99%