Gamma radiation induces senescence in human adult mesenchymal stem cells from bone marrow and periodontal ligaments

Ćmielová, Jana; Havelek, Radim; Soukup, Tomáš; Jiroutová, Alena; Víšek, Benjamin; Suchánek, J; Vávrová, Jiřina; Mokrý, Jaroslav; Muthná, Darina; Brůčková, Lenka; Filip, Stanislav; English, Denis; Řezáčová, Martina

doi:10.3109/09553002.2012.666001

Cited by 75 publications

(66 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5), transiently upregulated CDKN1A, CDKN2A, and TP53 (Supplemental Fig. 6) and other investigators demonstrated activation of the corresponding signaling cascades on a protein level (Cmielova et al 2012). DNAm profiles were compared before and 7 d after treatment with 15 Gy (n = 4).…”

Section: Gamma-irradiation Does Not Affect Dnammentioning

confidence: 95%

Pluripotent stem cells escape from senescence-associated DNA methylation changes

et al. 2012

View full text Add to dashboard Cite

Pluripotent stem cells evade replicative senescence, whereas other primary cells lose their proliferation and differentiation potential after a limited number of cell divisions, and this is accompanied by specific senescence-associated DNA methylation (SA-DNAm) changes. Here, we investigate SA-DNAm changes in mesenchymal stromal cells (MSC) upon longterm culture, irradiation-induced senescence, immortalization, and reprogramming into induced pluripotent stem cells (iPSC) using high-density HumanMethylation450 BeadChips. SA-DNAm changes are highly reproducible and they are enriched in intergenic and nonpromoter regions of developmental genes. Furthermore, SA-hypomethylation in particular appears to be associated with H3K9me3, H3K27me3, and Polycomb-group 2 target genes. We demonstrate that ionizing irradiation, although associated with a senescence phenotype, does not affect SA-DNAm. Furthermore, overexpression of the catalytic subunit of the human telomerase (TERT) or conditional immortalization with a doxycyclineinducible system (TERT and SV40-TAg) result in telomere extension, but do not prevent SA-DNAm. In contrast, we demonstrate that reprogramming into iPSC prevents almost the entire set of SA-DNAm changes. Our results indicate that long-term culture is associated with an epigenetically controlled process that stalls cells in a particular functional state, whereas irradiation-induced senescence and immortalization are not causally related to this process. Absence of SADNAm in pluripotent cells may play a central role for their escape from cellular senescence.

show abstract

Section: Gamma-irradiation Does Not Affect Dnammentioning

confidence: 95%

Pluripotent stem cells escape from senescence-associated DNA methylation changes

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Stem cell response to harmful stimuli is a prerequisite for the tissue repair and is under active examination (Cmielova et al 2012). In order to fulfill the task of tissue repair, stem cells must remain uninjured under unfavorable conditions.…”

Section: Introductionmentioning

confidence: 99%

“…Apoptosis seems to be a general outcome in embryonic stem cells subjected to various stress factors (Sokolov and Neumann 2013). On the other hand, a common stress response of various adult stem cells to different insults is stress-induced premature senescence (SIPS) (Toussaint et al 2000;Brandl et al 2011a, b;Cmielova et al 2012;Ko et al 2012), i.e., appearance of biomarkers of replicative senescence (RS). However, we did not find any indications that HS is also a SIPS trigger.…”

Section: Introductionmentioning

confidence: 99%

Sublethal heat shock induces premature senescence rather than apoptosis in human mesenchymal stem cells

Алексеенко

Zemelko

Домнина

et al. 2014

Cell Stress and Chaperones

View full text Add to dashboard Cite

Stem cells in adult organism are responsible for cell turnover and tissue regeneration. The study of stem cell stress response contributes to our knowledge on the mechanisms of damaged tissue repair. Previously, we demonstrated that sublethal heat shock (HS) induced apoptosis in human embryonic stem cells. This study aimed to investigate HS response of human adult stem cells. Human mesenchymal stem cells (MSCs) cultivated in vitro were challenged with sublethal HS. It was found that sublethal HS did not affect the cell viability assessed by annexin V/propidium staining. However, MSCs subjected to severe HS exhibited features of stress-induced premature senescence (SIPS): irreversible cell cycle arrest, altered morphology, increased expression of senescence-associated β-galactosidase (SA-β-gal) activity, and induction of cyclin-dependent kinase inhibitor p21 protein. High level of Hsp70 accumulation induced by sublethal HS did not return to the basal level, at least, after 72 h of the cell recovery when most cells exhibited SIPS hallmarks. MSCs survived sublethal HS, and resumed proliferation sustained the properties of parental MSCs: diploid karyotype, replicative senescence, expression of the cell surface markers, and capacity for multilineage differentiation. Our results showed for the first time that in human MSCs, sublethal HS induced premature senescence rather than apoptosis or necrosis. MSC progeny that survived sublethal HS manifested stem cell properties of the parental cells: limited replicative life span and multilineage capacity.

show abstract

“…O'Reilly et al (31) also demonstrated abnormalities in irradiated cultures a number of generations after initial exposure, including convolution of the nuclear envelope, increased incidence of microvilli and lysosomal accumulations, which are characteristic of apoptosis rather than necrosis. However, early senescence as an alternative cause of radiation-induced changes has been discussed for mesenchymal stem cells (MSCs) and fibroblasts (33,34).…”

Section: Discussionmentioning

confidence: 99%

Long-term changes in the properties of skin-derived fibroblasts following irradiation of the head and neck

et al. 2017

View full text Add to dashboard Cite

Abstract. The tumor stroma performs an important role in carcinogenesis. It predominantly consists of fibroblasts and the connective tissue produced by them, and undergoes a multitude of interactions with the surrounding cancer cells. Since irradiation is part of the majority of therapeutic strategies for head and neck squamous cell carcinoma, more information regarding the effects of a previous irradiation on the tumor stroma is desirable. In the present study, fibroblasts were cultivated from human non-irradiated and pre-irradiated skin of the neck for 48 h. Subsequently, analyses of cell viability, apoptosis, necrosis and motility were conducted via MTT assay, Annexin V/propidium iodide staining, electronic cell counting for 4 consecutive days, and scratch assay. Pre-irradiated fibroblasts exhibited a significantly slower growth rate as well as increased rates of apoptosis and necrosis. They also exhibited significantly decreased motility compared with non-irradiated fibroblasts. These results indicated the long-term effects of irradiation on fibroblasts, which may affect cancer recurrence in the irradiated region via the tumor stroma. More information, such as that regarding the secretory capacities of pre-irradiated fibroblasts, is required to evaluate the possible therapeutic implications of these findings.

show abstract

Gamma radiation induces senescence in human adult mesenchymal stem cells from bone marrow and periodontal ligaments

Abstract: Mesenchymal stem cells isolated from bone marrow and periodontal ligament respond to ionizing radiation by induction of stress-induced premature senescence without apparent differences in their radiation response.

Cited by 75 publications

References 40 publications

Pluripotent stem cells escape from senescence-associated DNA methylation changes

Pluripotent stem cells escape from senescence-associated DNA methylation changes

Sublethal heat shock induces premature senescence rather than apoptosis in human mesenchymal stem cells

Long-term changes in the properties of skin-derived fibroblasts following irradiation of the head and neck

Contact Info

Product

Resources

About