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Differential roles of hypoxia inducible factor subunits in multipotential stromal cells under hypoxic condition
Author(s) -
Tamama Kenichi,
Kawasaki Haruhisa,
Kerpedjieva Svetoslava S.,
Guan Jianjun,
Ganju Ramesh K.,
Sen Chandan K.
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22961
Subject(s) - paracrine signalling , microbiology and biotechnology , stromal cell , progenitor cell , adipogenesis , mesenchymal stem cell , hypoxia (environmental) , cellular differentiation , biology , hypoxia inducible factors , bone marrow , growth factor , stem cell , chemistry , cancer research , immunology , biochemistry , receptor , organic chemistry , oxygen , gene
Cell therapy with bone marrow multipotential stromal cells (MSCs) represents a promising approach to promote wound healing and tissue regeneration. MSCs expanded in vitro lose early progenitors with differentiation and therapeutic potentials under normoxic condition, whereas hypoxic condition promotes MSC self‐renewal through preserving colony forming early progenitors and maintaining undifferentiated phenotypes. Hypoxia inducible factor (HIF) pathway is a crucial signaling pathway activated in hypoxic condition. We evaluated the roles of HIFs in MSC differentiation, colony formation, and paracrine activity under hypoxic condition. Hypoxic condition reversibly decreased osteogenic and adipogenic differentiation. Decrease of osteogenic differentiation depended on HIF pathway; whereas decrease of adipogenic differentiation depended on the activation of unfolded protein response (UPR), but not HIFs. Hypoxia‐mediated increase of MSC colony formation was not HIF‐dependent also. Hypoxic exposure increased secretion of VEGF, HGF, and basic FGF in a HIF‐dependent manner. These findings suggest that HIF has a limited, but pivotal role in enhancing MSC self‐renewal and growth factor secretions under hypoxic condition. J. Cell. Biochem. 112: 804–817, 2011. © 2010 Wiley‐Liss, Inc.