Prolyl hydroxylase inhibitors act as agents to enhance the efficiency of cell therapy

In stem cell-based therapy as a subtype of regenerative medicine, stem cells can be used to replace or repair injured tissue and cells in order to treat disease. Stem cells have the ability to integrate into injured areas and produce new cells via processes of proliferation and differentiation. Several studies have demonstrated that hypoxia increases self-renewal, proliferation and post-homing differentiation of stem cells through the regulation of hypoxia-inducible factor-1 (HIF-1)-mediated gene expression. Thus, pharmacological interventions including prolyl hydroxylase (PHD) inhibitors are considered as promising solutions for stem cell-based therapy. PHD inhibitors stabilize the HIF-1 and activate its pathway through preventing proteasomal degradation of HIF-1.

This review focuses on the role of hypoxia, HIF-1 and especially PHD inhibitors on cell therapy. PHD structure and function are discussed as well as their inhibitors. In addition, we have investigated several preclinical studies in which PHD inhibitors improved the efficiency of cell-based therapies.

The data reviewed here suggest that PHD inhibitors are effective operators in improving stem cell therapy. However, because of some limitations, these compounds should be properly examined before clinical application.