PMID- 26332145
OWN - NLM
STAT- MEDLINE
DCOM- 20151120
LR  - 20200315
IS  - 1365-2184 (Electronic)
IS  - 0960-7722 (Print)
IS  - 0960-7722 (Linking)
VI  - 48
IP  - 5
DP  - 2015 Oct
TI  - Deferoxamine preconditioning to restore impaired HIF-1alpha-mediated angiogenic 
      mechanisms in adipose-derived stem cells from STZ-induced type 1 diabetic rats.
PG  - 532-49
LID - 10.1111/cpr.12209 [doi]
AB  - OBJECTIVES: Both excessive and insufficient angiogenesis are associated with 
      progression of diabetic complications, of which poor angiogenesis is an important 
      feature. Currently, adipose-derived stem cells (ADSCs) are considered to be a 
      promising source to aid therapeutic neovascularization. However, functionality of 
      these cells is impaired by diabetes which can result from a defect in 
      hypoxia-inducible factor-1 (HIF-1), a key mediator involved in 
      neovascularization. In the current study, we sought to explore effectiveness of 
      pharmacological priming with deferoxamine (DFO) as a hypoxia mimetic agent, to 
      restore the compromised angiogenic pathway, with the aid of ADSCs derived from 
      streptozotocin (STZ)-induced type 1 diabetic rats ('diabetic ADSCs'). MATERIALS 
      AND METHODS: Diabetic ADSCs were treated with DFO and compared to normal and 
      non-treated diabetic ADSCs for expression of HIF-1alpha, VEGF, FGF-2 and SDF-1, at 
      mRNA and protein levels, using qRT-PCR, western blotting and ELISA assay. 
      Activity of matrix metalloproteinases -2 and -9 were measured using a gelatin 
      zymography assay. Angiogenic potential of conditioned media derived from normal, 
      DFO-treated and non-treated diabetic ADSCs were determined by in vitro (in 
      HUVECs) and in vivo experiments including scratch assay, three-dimensional tube 
      formation testing and surgical wound healing models. RESULTS: DFO remarkably 
      enhanced expression of noted genes by mRNA and protein levels and restored 
      activity of matrix metalloproteinases -2 and -9. Compromised angiogenic potential 
      of conditioned medium derived from diabetic ADSCs was restored by DFO both 
      in vitro and in vivo experiments. CONCLUSION: DFO preconditioning restored 
      neovascularization potential of ADSCs derived from diabetic rats by affecting the 
      HIF-1alpha pathway.
CI  - (c) 2015 John Wiley & Sons Ltd.
FAU - Mehrabani, M
AU  - Mehrabani M
AD  - Razi Drug Research Center, Department of pharmacology, Iran University of Medical 
      Sciences, Tehran, Iran.
FAU - Najafi, M
AU  - Najafi M
AD  - Department of Biochemistry, Iran University of Medical Sciences, Tehran, Iran.
FAU - Kamarul, T
AU  - Kamarul T
AD  - Tissue Engineering Group (TEG) & Research, National Orthopedic Centre of 
      Excellence in Research & Learning (NOCERAL), Department of Orthopedics, Faculty 
      of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
FAU - Mansouri, K
AU  - Mansouri K
AD  - Medical Biology Research Center, Kermanshah University of Medical Sciences, 
      Kermanshah, Iran.
FAU - Iranpour, M
AU  - Iranpour M
AD  - Department of Pathology, Kerman University of Medical Sciences, Kerman, Iran.
FAU - Nematollahi, M H
AU  - Nematollahi MH
AD  - Department of Biochemistry, Kerman University of Medical Sciences, Kerman, Iran.
FAU - Ghazi-Khansari, M
AU  - Ghazi-Khansari M
AD  - Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran.
FAU - Sharifi, A M
AU  - Sharifi AM
AD  - Razi Drug Research Center, Department of pharmacology, Iran University of Medical 
      Sciences, Tehran, Iran.
AD  - Department of Tissue Engineering and regenerative Medicine, School of Advanced 
      Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cell Prolif
JT  - Cell proliferation
JID - 9105195
RN  - 0 (CXCL12 protein, rat)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 5W494URQ81 (Streptozocin)
RN  - J06Y7MXW4D (Deferoxamine)
SB  - IM
MH  - Adipose Tissue/cytology
MH  - Animals
MH  - Cell Movement/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chemokine CXCL12/genetics/metabolism
MH  - Deferoxamine/*pharmacology
MH  - Diabetes Mellitus, Experimental/chemically induced/pathology
MH  - Fibroblast Growth Factor 2/genetics/metabolism
MH  - Human Umbilical Vein Endothelial Cells
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Male
MH  - Neovascularization, Physiologic/*drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Stem Cells/cytology/*drug effects/metabolism
MH  - Streptozocin/toxicity
MH  - Vascular Endothelial Growth Factor A/genetics/metabolism
MH  - Wound Healing/drug effects
PMC - PMC6495947
COIS- The authors confirm that there are no conflicts of interest.
EDAT- 2015/09/04 06:00
MHDA- 2015/12/15 06:00
PMCR- 2015/09/02
CRDT- 2015/09/03 06:00
PHST- 2015/02/23 00:00 [received]
PHST- 2015/06/22 00:00 [accepted]
PHST- 2015/09/03 06:00 [entrez]
PHST- 2015/09/04 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2015/09/02 00:00 [pmc-release]
AID - CPR12209 [pii]
AID - 10.1111/cpr.12209 [doi]
PST - ppublish
SO  - Cell Prolif. 2015 Oct;48(5):532-49. doi: 10.1111/cpr.12209.