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


METHODS
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.


CONCLUSIONS
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.
a 1 Research center for molecular medicine, Hamadan University of Medical Sciences , Hamadan, the Islamic Republic of Iran najafi2535@gmail.com.
Maryam
M
Esfahani
a 1 Research center for molecular medicine, Hamadan University of Medical Sciences , Hamadan, the Islamic Republic of Iran najafi2535@gmail.com.
Fatemeh
F
Karimi
a 1 Research center for molecular medicine, Hamadan University of Medical Sciences , Hamadan, the Islamic Republic of Iran najafi2535@gmail.com.
Saeid
S
Afshar
b 2 Shahid Beheshti University of Medical Science, Hearing Disorders Research Center , Tehran, the Islamic Republic of Iran.
Somayeh
S
Niknazar
a 1 Research center for molecular medicine, Hamadan University of Medical Sciences , Hamadan, the Islamic Republic of Iran najafi2535@gmail.com.
Sareh
S
Sohrabi
a 1 Research center for molecular medicine, Hamadan University of Medical Sciences , Hamadan, the Islamic Republic of Iran najafi2535@gmail.com.
Rezvan
R
Najafi
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods* / Q000639:trends; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000235:genetics; D064800:Prolyl-Hydroxylase Inhibitors / Q000008:administration & dosage*; D033581:Stem Cell Transplantation / Q000379:methods / Q000639:trends; D016896:Treatment Outcome
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D064800:Prolyl-Hydroxylase Inhibitors
hypoxia; hypoxia-inducible factor-1; prolyl hydroxylase inhibitors; stem cell therapy