Oxidative stress induces senescence in human mesenchymal stem cells

Mesenchymal stem cells (MSCs) contribute to tissue repair in vivo and form an attractive cell source for tissue engineering. Their regenerative potential is impaired by cellular senescence. The effects of oxidative stress on MSCs are still unknown. Our studies were to investigate into the proliferat...

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Published in	Experimental cell research Vol. 317; no. 11; pp. 1541 - 1547
Main Authors	Brandl, Anita, Meyer, Matthias, Bechmann, Volker, Nerlich, Michael, Angele, Peter
Format	Journal Article
Language	English
Published	United States Elsevier Inc 01.07.2011 Elsevier BV
Subjects	60 APPLIED LIFE SCIENCES Adult AGING beta-galactosidase beta-Galactosidase - metabolism CELL PROLIFERATION Cell Proliferation - drug effects Cells, Cultured Cellular biology Cellular Senescence chondrocytes DNA damage DNA DAMAGES FIBROBLASTS Fibroblasts - cytology Fibroblasts - drug effects Fibroblasts - metabolism GALACTOSIDASE gene expression Gene Expression Profiling Human mesenchymal stem cells Humans HYDROGEN PEROXIDE Hydrogen Peroxide - pharmacology IN VIVO LETHAL DOSES Mesenchymal Stromal Cells - metabolism MONOCLINIC LATTICES oxidants Oxidants - pharmacology OXIDATION Oxidative Stress PHOSPHATES Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics SODIUM COMPOUNDS STEM CELLS stress response stress tolerance Telomere Telomeres tissue engineering tissue repair Up-Regulation Oxidative stress SSC DNA damage Cellular senescence TRF Human mesenchymal stem cells SAβ-gal SD Telomeres MSCs cpd DPBS SIRT
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Abstract	Mesenchymal stem cells (MSCs) contribute to tissue repair in vivo and form an attractive cell source for tissue engineering. Their regenerative potential is impaired by cellular senescence. The effects of oxidative stress on MSCs are still unknown. Our studies were to investigate into the proliferation potential, cytological features and the telomere linked stress response system of MSCs, subject to acute or prolonged oxidant challenge with hydrogen peroxide. Telomere length was measured using the telomere restriction fragment assay, gene expression was determined by rtPCR. Sub-lethal doses of oxidative stress reduced proliferation rates and induced senescent-morphological features and senescence-associated β-galactosidase positivity. Prolonged low dose treatment with hydrogen peroxide had no effects on cell proliferation or morphology. Sub-lethal and prolonged low doses of oxidative stress considerably accelerated telomere attrition. Following acute oxidant insult p21 was up-regulated prior to returning to initial levels. TRF1 was significantly reduced, TRF2 showed a slight up-regulation. SIRT1 and XRCC5 were up-regulated after oxidant insult and expression levels increased in aging cells. Compared to fibroblasts and chondrocytes, MSCs showed an increased tolerance to oxidative stress regarding proliferation, telomere biology and gene expression with an impaired stress tolerance in aged cells.
AbstractList	Mesenchymal stem cells (MSCs) contribute to tissue repair in vivo and form an attractive cell source for tissue engineering. Their regenerative potential is impaired by cellular senescence. The effects of oxidative stress on MSCs are still unknown. Our studies were to investigate into the proliferation potential, cytological features and the telomere linked stress response system of MSCs, subject to acute or prolonged oxidant challenge with hydrogen peroxide. Telomere length was measured using the telomere restriction fragment assay, gene expression was determined by rtPCR. Sub-lethal doses of oxidative stress reduced proliferation rates and induced senescent-morphological features and senescence-associated β-galactosidase positivity. Prolonged low dose treatment with hydrogen peroxide had no effects on cell proliferation or morphology. Sub-lethal and prolonged low doses of oxidative stress considerably accelerated telomere attrition. Following acute oxidant insult p21 was up-regulated prior to returning to initial levels. TRF1 was significantly reduced, TRF2 showed a slight up-regulation. SIRT1 and XRCC5 were up-regulated after oxidant insult and expression levels increased in aging cells. Compared to fibroblasts and chondrocytes, MSCs showed an increased tolerance to oxidative stress regarding proliferation, telomere biology and gene expression with an impaired stress tolerance in aged cells. Mesenchymal stem cells (MSCs) contribute to tissue repair in vivo and form an attractive cell source for tissue engineering. Their regenerative potential is impaired by cellular senescence. The effects of oxidative stress on MSCs are still unknown. Our studies were to investigate into the proliferation potential, cytological features and the telomere linked stress response system of MSCs, subject to acute or prolonged oxidant challenge with hydrogen peroxide. Telomere length was measured using the telomere restriction fragment assay, gene expression was determined by rtPCR. Sub-lethal doses of oxidative stress reduced proliferation rates and induced senescent-morphological features and senescence-associated {beta}-galactosidase positivity. Prolonged low dose treatment with hydrogen peroxide had no effects on cell proliferation or morphology. Sub-lethal and prolonged low doses of oxidative stress considerably accelerated telomere attrition. Following acute oxidant insult p21 was up-regulated prior to returning to initial levels. TRF1 was significantly reduced, TRF2 showed a slight up-regulation. SIRT1 and XRCC5 were up-regulated after oxidant insult and expression levels increased in aging cells. Compared to fibroblasts and chondrocytes, MSCs showed an increased tolerance to oxidative stress regarding proliferation, telomere biology and gene expression with an impaired stress tolerance in aged cells. Mesenchymal stem cells (MSCs) contribute to tissue repair in vivo and form an attractive cell source for tissue engineering. Their regenerative potential is impaired by cellular senescence. The effects of oxidative stress on MSCs are still unknown. Our studies were to investigate into the proliferation potential, cytological features and the telomere linked stress response system of MSCs, subject to acute or prolonged oxidant challenge with hydrogen peroxide. Telomere length was measured using the telomere restriction fragment assay, gene expression was determined by rtPCR. Sub-lethal doses of oxidative stress reduced proliferation rates and induced senescent-morphological features and senescence-associated [beta]-galactosidase positivity. Prolonged low dose treatment with hydrogen peroxide had no effects on cell proliferation or morphology. Sub-lethal and prolonged low doses of oxidative stress considerably accelerated telomere attrition. Following acute oxidant insult p21 was up-regulated prior to returning to initial levels. TRF1 was significantly reduced, TRF2 showed a slight up-regulation. SIRT1 and XRCC5 were up-regulated after oxidant insult and expression levels increased in aging cells. Compared to fibroblasts and chondrocytes, MSCs showed an increased tolerance to oxidative stress regarding proliferation, telomere biology and gene expression with an impaired stress tolerance in aged cells. [PUBLICATION ABSTRACT] Mesenchymal stem cells (MSCs) contribute to tissue repair in vivo and form an attractive cell source for tissue engineering. Their regenerative potential is impaired by cellular senescence. The effects of oxidative stress on MSCs are still unknown. Our studies were to investigate into the proliferation potential, cytological features and the telomere linked stress response system of MSCs, subject to acute or prolonged oxidant challenge with hydrogen peroxide. Telomere length was measured using the telomere restriction fragment assay, gene expression was determined by rtPCR. Sub-lethal doses of oxidative stress reduced proliferation rates and induced senescent-morphological features and senescence-associated β-galactosidase positivity. Prolonged low dose treatment with hydrogen peroxide had no effects on cell proliferation or morphology. Sub-lethal and prolonged low doses of oxidative stress considerably accelerated telomere attrition. Following acute oxidant insult p21 was up-regulated prior to returning to initial levels. TRF1 was significantly reduced, TRF2 showed a slight up-regulation. SIRT1 and XRCC5 were up-regulated after oxidant insult and expression levels increased in aging cells. Compared to fibroblasts and chondrocytes, MSCs showed an increased tolerance to oxidative stress regarding proliferation, telomere biology and gene expression with an impaired stress tolerance in aged cells.Mesenchymal stem cells (MSCs) contribute to tissue repair in vivo and form an attractive cell source for tissue engineering. Their regenerative potential is impaired by cellular senescence. The effects of oxidative stress on MSCs are still unknown. Our studies were to investigate into the proliferation potential, cytological features and the telomere linked stress response system of MSCs, subject to acute or prolonged oxidant challenge with hydrogen peroxide. Telomere length was measured using the telomere restriction fragment assay, gene expression was determined by rtPCR. Sub-lethal doses of oxidative stress reduced proliferation rates and induced senescent-morphological features and senescence-associated β-galactosidase positivity. Prolonged low dose treatment with hydrogen peroxide had no effects on cell proliferation or morphology. Sub-lethal and prolonged low doses of oxidative stress considerably accelerated telomere attrition. Following acute oxidant insult p21 was up-regulated prior to returning to initial levels. TRF1 was significantly reduced, TRF2 showed a slight up-regulation. SIRT1 and XRCC5 were up-regulated after oxidant insult and expression levels increased in aging cells. Compared to fibroblasts and chondrocytes, MSCs showed an increased tolerance to oxidative stress regarding proliferation, telomere biology and gene expression with an impaired stress tolerance in aged cells.
Author	Brandl, Anita Bechmann, Volker Meyer, Matthias Nerlich, Michael Angele, Peter
Author_xml	– sequence: 1 givenname: Anita surname: Brandl fullname: Brandl, Anita organization: Department of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany – sequence: 2 givenname: Matthias surname: Meyer fullname: Meyer, Matthias organization: Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany – sequence: 3 givenname: Volker surname: Bechmann fullname: Bechmann, Volker organization: Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany – sequence: 4 givenname: Michael surname: Nerlich fullname: Nerlich, Michael organization: Department of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany – sequence: 5 givenname: Peter surname: Angele fullname: Angele, Peter email: Peter.Angele@klinik.uni-regensburg.de organization: Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany
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Keywords	Oxidative stress SSC DNA damage Cellular senescence TRF Human mesenchymal stem cells SAβ-gal SD Telomeres MSCs cpd DPBS SIRT
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Snippet	Mesenchymal stem cells (MSCs) contribute to tissue repair in vivo and form an attractive cell source for tissue engineering. Their regenerative potential is...
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SubjectTerms	60 APPLIED LIFE SCIENCES Adult AGING beta-galactosidase beta-Galactosidase - metabolism CELL PROLIFERATION Cell Proliferation - drug effects Cells, Cultured Cellular biology Cellular Senescence chondrocytes DNA damage DNA DAMAGES FIBROBLASTS Fibroblasts - cytology Fibroblasts - drug effects Fibroblasts - metabolism GALACTOSIDASE gene expression Gene Expression Profiling Human mesenchymal stem cells Humans HYDROGEN PEROXIDE Hydrogen Peroxide - pharmacology IN VIVO LETHAL DOSES Mesenchymal Stromal Cells - metabolism MONOCLINIC LATTICES oxidants Oxidants - pharmacology OXIDATION Oxidative Stress PHOSPHATES Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics SODIUM COMPOUNDS STEM CELLS stress response stress tolerance Telomere Telomeres tissue engineering tissue repair Up-Regulation
Title	Oxidative stress induces senescence in human mesenchymal stem cells
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