Role of p16INK4a and BMI-1 in oxidative stress-induced premature senescence in human dental pulp stem cells
Human dental pulp stem cells (hDPSCs) are a source for cell therapy. Before implantation, an in vitro expansion step is necessary, with the inconvenience that hDPSCs undergo senescence following a certain number of passages, loosing their stemness properties. Long-term in vitro culture of hDPSCs at...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-08-01
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| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231717301738 |
| _version_ | 1828422436636327936 |
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| author | Cristina Mas-Bargues José Viña-Almunia Marta Inglés Jorge Sanz-Ros Juan Gambini José Santiago Ibáñez-Cabellos José Luis García-Giménez José Viña Consuelo Borrás |
| author_facet | Cristina Mas-Bargues José Viña-Almunia Marta Inglés Jorge Sanz-Ros Juan Gambini José Santiago Ibáñez-Cabellos José Luis García-Giménez José Viña Consuelo Borrás |
| author_sort | Cristina Mas-Bargues |
| collection | DOAJ |
| description | Human dental pulp stem cells (hDPSCs) are a source for cell therapy. Before implantation, an in vitro expansion step is necessary, with the inconvenience that hDPSCs undergo senescence following a certain number of passages, loosing their stemness properties. Long-term in vitro culture of hDPSCs at 21% (ambient oxygen tension) compared with 3–6% oxygen tension (physiological oxygen tension) caused an oxidative stress-related premature senescence, as evidenced by increased β-galactosidase activity and increased lysil oxidase expression, which is mediated by p16INK4a pathway. Furthermore, hDPSCs cultured at 21% oxygen tension underwent a downregulation of OCT4, SOX2, KLF4 and c-MYC factors, which was recued by BMI-1 silencing. Thus, p16INK4a and BMI-1 might play a role in the oxidative stress-associated premature senescence. We show that it is important for clinical applications to culture cells at physiological pO2 to retain their stemness characteristics and to delay senescence. Keywords: Oxygen tension, Regenerative medicine, Aging |
| first_indexed | 2024-12-10T15:47:17Z |
| format | Article |
| id | doaj.art-bcfd442efcb24c719b8a32b3d4aa473c |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-10T15:47:17Z |
| publishDate | 2017-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-bcfd442efcb24c719b8a32b3d4aa473c2022-12-22T01:42:55ZengElsevierRedox Biology2213-23172017-08-0112690698Role of p16INK4a and BMI-1 in oxidative stress-induced premature senescence in human dental pulp stem cellsCristina Mas-Bargues0José Viña-Almunia1Marta Inglés2Jorge Sanz-Ros3Juan Gambini4José Santiago Ibáñez-Cabellos5José Luis García-Giménez6José Viña7Consuelo Borrás8Department of Physiology. Faculty of Medicine and Dentistry. University of Valencia, Av/ Blasco Ibáñez, 15, 46010 Valencia, Spain; INCLIVA Health Research Institute, Av/ de Menéndez y Pelayo, 4, 46010 Valencia, Spain; Center for Biomedical Network Research on Frailty and Healthy Aging (CIBERFES), CIBER-ISCIII, SpainDepartment of Stomatology. Faculty of Medicine and Dentistry. University of Valencia, Av/ Blasco Ibáñez, 15, 46010 Valencia, SpainDepartment of Physiotherapy. Faculty of Medicine and Dentistry. University of Valencia, Av/ Blasco Ibáñez, 15, 46010 Valencia, Spain; INCLIVA Health Research Institute, Av/ de Menéndez y Pelayo, 4, 46010 Valencia, Spain; Center for Biomedical Network Research on Frailty and Healthy Aging (CIBERFES), CIBER-ISCIII, SpainDepartment of Physiology. Faculty of Medicine and Dentistry. University of Valencia, Av/ Blasco Ibáñez, 15, 46010 Valencia, Spain; INCLIVA Health Research Institute, Av/ de Menéndez y Pelayo, 4, 46010 Valencia, Spain; Center for Biomedical Network Research on Frailty and Healthy Aging (CIBERFES), CIBER-ISCIII, SpainDepartment of Physiology. Faculty of Medicine and Dentistry. University of Valencia, Av/ Blasco Ibáñez, 15, 46010 Valencia, Spain; INCLIVA Health Research Institute, Av/ de Menéndez y Pelayo, 4, 46010 Valencia, Spain; Center for Biomedical Network Research on Frailty and Healthy Aging (CIBERFES), CIBER-ISCIII, SpainDepartment of Physiology. Faculty of Medicine and Dentistry. University of Valencia, Av/ Blasco Ibáñez, 15, 46010 Valencia, Spain; Center for Biomedical Network Research on Rare Diseases (CIBERER), CIBER-ISCIII, Spain; INCLIVA Health Research Institute, Av/ de Menéndez y Pelayo, 4, 46010 Valencia, SpainDepartment of Physiology. Faculty of Medicine and Dentistry. University of Valencia, Av/ Blasco Ibáñez, 15, 46010 Valencia, Spain; Center for Biomedical Network Research on Rare Diseases (CIBERER), CIBER-ISCIII, Spain; INCLIVA Health Research Institute, Av/ de Menéndez y Pelayo, 4, 46010 Valencia, SpainDepartment of Physiology. Faculty of Medicine and Dentistry. University of Valencia, Av/ Blasco Ibáñez, 15, 46010 Valencia, Spain; INCLIVA Health Research Institute, Av/ de Menéndez y Pelayo, 4, 46010 Valencia, Spain; Center for Biomedical Network Research on Frailty and Healthy Aging (CIBERFES), CIBER-ISCIII, SpainDepartment of Physiology. Faculty of Medicine and Dentistry. University of Valencia, Av/ Blasco Ibáñez, 15, 46010 Valencia, Spain; INCLIVA Health Research Institute, Av/ de Menéndez y Pelayo, 4, 46010 Valencia, Spain; Center for Biomedical Network Research on Frailty and Healthy Aging (CIBERFES), CIBER-ISCIII, Spain; Corresponding author at: Department of Physiology, Faculty of Medicine, Avenida Blasco Ibañez 15, 46010 Valencia, Spain.Human dental pulp stem cells (hDPSCs) are a source for cell therapy. Before implantation, an in vitro expansion step is necessary, with the inconvenience that hDPSCs undergo senescence following a certain number of passages, loosing their stemness properties. Long-term in vitro culture of hDPSCs at 21% (ambient oxygen tension) compared with 3–6% oxygen tension (physiological oxygen tension) caused an oxidative stress-related premature senescence, as evidenced by increased β-galactosidase activity and increased lysil oxidase expression, which is mediated by p16INK4a pathway. Furthermore, hDPSCs cultured at 21% oxygen tension underwent a downregulation of OCT4, SOX2, KLF4 and c-MYC factors, which was recued by BMI-1 silencing. Thus, p16INK4a and BMI-1 might play a role in the oxidative stress-associated premature senescence. We show that it is important for clinical applications to culture cells at physiological pO2 to retain their stemness characteristics and to delay senescence. Keywords: Oxygen tension, Regenerative medicine, Aginghttp://www.sciencedirect.com/science/article/pii/S2213231717301738 |
| spellingShingle | Cristina Mas-Bargues José Viña-Almunia Marta Inglés Jorge Sanz-Ros Juan Gambini José Santiago Ibáñez-Cabellos José Luis García-Giménez José Viña Consuelo Borrás Role of p16INK4a and BMI-1 in oxidative stress-induced premature senescence in human dental pulp stem cells Redox Biology |
| title | Role of p16INK4a and BMI-1 in oxidative stress-induced premature senescence in human dental pulp stem cells |
| title_full | Role of p16INK4a and BMI-1 in oxidative stress-induced premature senescence in human dental pulp stem cells |
| title_fullStr | Role of p16INK4a and BMI-1 in oxidative stress-induced premature senescence in human dental pulp stem cells |
| title_full_unstemmed | Role of p16INK4a and BMI-1 in oxidative stress-induced premature senescence in human dental pulp stem cells |
| title_short | Role of p16INK4a and BMI-1 in oxidative stress-induced premature senescence in human dental pulp stem cells |
| title_sort | role of p16ink4a and bmi 1 in oxidative stress induced premature senescence in human dental pulp stem cells |
| url | http://www.sciencedirect.com/science/article/pii/S2213231717301738 |
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