Cellular and molecular stimulation of adipose-derived stem cells under hypoxia

Sangjin Kang, Soo Min Kim, Jong Hyuk Sung

Research output: Contribution to journalReview article

19 Citations (Scopus)

Abstract

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-1a 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.

Original languageEnglish
Pages (from-to)553-562
Number of pages10
JournalCell Biology International
Volume38
Issue number5
DOIs
Publication statusPublished - 2014 Jan 1

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Cell Hypoxia
Stem Cells
Non-Receptor Type 2 Protein Tyrosine Phosphatase
Reactive Oxygen Species
Phosphorylation
Platelet-Derived Growth Factor beta Receptor
Cell- and Tissue-Based Therapy
Vascular Endothelial Growth Factor A
Up-Regulation
Down-Regulation
Hypoxia

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

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Cellular and molecular stimulation of adipose-derived stem cells under hypoxia. / Kang, Sangjin; Kim, Soo Min; Sung, Jong Hyuk.

In: Cell Biology International, Vol. 38, No. 5, 01.01.2014, p. 553-562.

Research output: Contribution to journalReview article

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AB - 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-1a 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.

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