Chemical Activation of the Hypoxia-Inducible Factor Reversibly Reduces Tendon Stem Cell Proliferation, Inhibits Their Differentiation, and Maintains Cell Undifferentiation
Adult stem cell-based therapeutic approaches for tissue regeneration have been proposed for several years. However, adult stem cells are usually limited in number and difficult to be expanded in vitro, and they usually tend to quickly lose their potency with passages, as they differentiate and becom...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2018/9468085 |
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| author | Alessandra Menon Pasquale Creo Marco Piccoli Sonia Bergante Erika Conforti Giuseppe Banfi Pietro Randelli Luigi Anastasia |
| author_facet | Alessandra Menon Pasquale Creo Marco Piccoli Sonia Bergante Erika Conforti Giuseppe Banfi Pietro Randelli Luigi Anastasia |
| author_sort | Alessandra Menon |
| collection | DOAJ |
| description | Adult stem cell-based therapeutic approaches for tissue regeneration have been proposed for several years. However, adult stem cells are usually limited in number and difficult to be expanded in vitro, and they usually tend to quickly lose their potency with passages, as they differentiate and become senescent. Culturing stem cells under reduced oxygen tensions (below 21%) has been proposed as a tool to increase cell proliferation, but many studies reported opposite effects. In particular, cell response to hypoxia seems to be very stem cell type specific. Nonetheless, it is clear that a major role in this process is played by the hypoxia inducible factor (HIF), the master regulator of cell response to oxygen deprivation, which affects cell metabolism and differentiation. Herein, we report that a chemical activation of HIF in human tendon stem cells reduces their proliferation and inhibits their differentiation in a reversible and dose-dependent manner. These results support the notion that hypoxia, by activating HIF, plays a crucial role in preserving stem cells in an undifferentiated state in the “hypoxic niches” present in the tissue in which they reside before migrating in more oxygenated areas to heal a damaged tissue. |
| format | Article |
| id | doaj-art-0312545ae0484ce9abe51647319233e2 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-0312545ae0484ce9abe51647319233e22025-02-03T01:02:30ZengWileyStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/94680859468085Chemical Activation of the Hypoxia-Inducible Factor Reversibly Reduces Tendon Stem Cell Proliferation, Inhibits Their Differentiation, and Maintains Cell UndifferentiationAlessandra Menon0Pasquale Creo1Marco Piccoli2Sonia Bergante3Erika Conforti4Giuseppe Banfi5Pietro Randelli6Luigi Anastasia7IRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyIRCCS Istituto Ortopedico Galeazzi, Milan, ItalyIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyAdult stem cell-based therapeutic approaches for tissue regeneration have been proposed for several years. However, adult stem cells are usually limited in number and difficult to be expanded in vitro, and they usually tend to quickly lose their potency with passages, as they differentiate and become senescent. Culturing stem cells under reduced oxygen tensions (below 21%) has been proposed as a tool to increase cell proliferation, but many studies reported opposite effects. In particular, cell response to hypoxia seems to be very stem cell type specific. Nonetheless, it is clear that a major role in this process is played by the hypoxia inducible factor (HIF), the master regulator of cell response to oxygen deprivation, which affects cell metabolism and differentiation. Herein, we report that a chemical activation of HIF in human tendon stem cells reduces their proliferation and inhibits their differentiation in a reversible and dose-dependent manner. These results support the notion that hypoxia, by activating HIF, plays a crucial role in preserving stem cells in an undifferentiated state in the “hypoxic niches” present in the tissue in which they reside before migrating in more oxygenated areas to heal a damaged tissue.http://dx.doi.org/10.1155/2018/9468085 |
| spellingShingle | Alessandra Menon Pasquale Creo Marco Piccoli Sonia Bergante Erika Conforti Giuseppe Banfi Pietro Randelli Luigi Anastasia Chemical Activation of the Hypoxia-Inducible Factor Reversibly Reduces Tendon Stem Cell Proliferation, Inhibits Their Differentiation, and Maintains Cell Undifferentiation Stem Cells International |
| title | Chemical Activation of the Hypoxia-Inducible Factor Reversibly Reduces Tendon Stem Cell Proliferation, Inhibits Their Differentiation, and Maintains Cell Undifferentiation |
| title_full | Chemical Activation of the Hypoxia-Inducible Factor Reversibly Reduces Tendon Stem Cell Proliferation, Inhibits Their Differentiation, and Maintains Cell Undifferentiation |
| title_fullStr | Chemical Activation of the Hypoxia-Inducible Factor Reversibly Reduces Tendon Stem Cell Proliferation, Inhibits Their Differentiation, and Maintains Cell Undifferentiation |
| title_full_unstemmed | Chemical Activation of the Hypoxia-Inducible Factor Reversibly Reduces Tendon Stem Cell Proliferation, Inhibits Their Differentiation, and Maintains Cell Undifferentiation |
| title_short | Chemical Activation of the Hypoxia-Inducible Factor Reversibly Reduces Tendon Stem Cell Proliferation, Inhibits Their Differentiation, and Maintains Cell Undifferentiation |
| title_sort | chemical activation of the hypoxia inducible factor reversibly reduces tendon stem cell proliferation inhibits their differentiation and maintains cell undifferentiation |
| url | http://dx.doi.org/10.1155/2018/9468085 |
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