Mesenchymal stem cells cultured under hypoxia escape from senescence via down-regulation of p16 and extracellular signal regulated kinase

Journal Article · Fri Jan 15 00:00:00 EST 2010 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2009.12.096· OSTI ID:22202330

Jin, Yonghui; Kato, Tomohisa; Furu, Moritoshi ^[1]; Nasu, Akira ^[1]; Kajita, Yoichiro ^[1]; Mitsui, Hiroto ^[1]; Ueda, Michiko ^[1]; Aoyama, Tomoki ^[2]; Nakayama, Tomitaka; Nakamura, Takashi ^[3]; Toguchida, Junya ^[1]

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1. Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University (Japan)
2. Human Health Sciences, Graduate School of Medicine, Kyoto University (Japan)
3. Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University (Japan)

Hypoxia has been considered to affect the properties of tissue stem cells including mesenchymal stem cells (MSCs). Effects of long periods of exposure to hypoxia on human MSCs, however, have not been clearly demonstrated. MSCs cultured under normoxic conditions (20% pO{sub 2}) ceased to proliferate after 15-25 population doublings, while MSCs cultured under hypoxic conditions (1% pO{sub 2}) retained the ability to proliferate with an additional 8-20 population doublings. Most of the MSCs cultured under normoxic conditions were in a senescent state after 100 days, while few senescent cells were found in the hypoxic culture, which was associated with a down-regulation of p16 gene expression. MSCs cultured for 100 days under hypoxic conditions were superior to those cultured under normoxic conditions in the ability to differentiate into the chondro- and adipogenic, but not osteogenic, lineage. Among the molecules related to mitogen-activated protein kinase (MAPK) signaling pathways, extracellular signal regulated kinase (ERK) was significantly down-regulated by hypoxia, which helped to inhibit the up-regulation of p16 gene expression. Therefore, the hypoxic culture retained MSCs in an undifferentiated and senescence-free state through the down-regulation of p16 and ERK.

• OSTI ID: 22202330
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 391, Issue 3; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL TISSUES
ANOXIA
GENE REGULATION
GENES
OXYGEN
PARTIAL PRESSURE
PROTEINS
STEM CELLS