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Cellular and molecular stimulation of adipose‐derived stem cells under hypoxia
Author(s) -
Kang Sangjin,
Kim SooMin,
Sung JongHyuk
Publication year - 2014
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10246
Subject(s) - adipose tissue , stimulation , hypoxia (environmental) , microbiology and biotechnology , stem cell , chemistry , biology , neuroscience , biochemistry , oxygen , organic chemistry
Cultivation under hypoxia has beneficial effects on adipose‐derived stem cells (ASCs). Despite a history of extensive research on the responses of ASCs to hypoxia, investigations have focused on functional alterations of ASCs. Therefore, we provide novel insight in this review into the cellular and molecular changes that occur in ASCs under hypoxic conditions. Hypoxia increases the proliferation and migration of ASCs by the generation of reactive oxygen species (ROS) and downstream phosphorylation of platelet‐derived growth factor receptor‐beta, ERK1/2, and Akt. Chronically, activation of these signaling pathways upregulates miR‐210 via phosphorylation of NF‐κB and Elk1. Protein tyrosine phosphatase, non‐receptor type 2 (PTPN2) is a direct miR‐210 target, and downregulation of PTPN2 mediates the proliferation and migration of ASCs during hypoxia. In addition, the paracrine effect of ASCs is enhanced under hypoxic conditions, irrespective of whether ROS are generated. Hypoxic preconditioning stabilizes hypoxia inducible factor‐1α under hypoxic conditions and increases secretion of vascular endothelial growth factor, thereby improving the regenerative potential of ASCs. Therefore, understanding the cellular and molecular changes that occur during hypoxia is highly relevant for the development of novel ASC therapies.