Chemically primed bone-marrow derived mesenchymal stem cells show enhanced expression of chemokine receptors contributed to their migration capability.
OBJECTIVE
The limited homing potential of bone-marrow-derived mesenchymal stem cells (BM-MSC) is the key obstacle in MSC-based therapy. It is believed that chemokines and chemokine receptor interactions play key roles in cellular processes associated with migration. Meanwhile, MSCs express a low level of distinct chemokine receptors and they even lose these receptors on their surface after a few passages which influence their therapeutic applications negatively. This study investigated whether treatment of BM-MSCs with hypoxia-mimicking agents would increase expression of some chemokine receptors and cell migration.


METHODS
BM-MSCs were treated at passage 2 for our gene expression profiling. All qPCR experiments were performed by SYBR Green method in CFX-96 Bio-Rad Real-Time PCR. The Boyden chamber assay was utilized to investigate BM-MSC homing.


RESULTS
Possible approaches to increasing the expression level of chemokine receptors by different hypoxia-mimicking agents such as valproic acid (VPA), CoCl2, and desferrioxamine (DFX) are described. Results show DFX efficiently up-regulate the CXCR7 and CXCR4 gene expression while VPA increase only the CXCR7 gene expression and no significant change in expression level of CXCR4 and the CXCR7 gene was detectable by CoCl2 treatment. Chemotaxis assay results show that pre-treatment with DFX, VPA, and Cocl2 enhances significantly the migration ability of BM-MSCs compared with the untreated control group and DFX treatment accelerates MSCs homing significantly with a higher rate than VPA and Cocl2 treatments.


CONCLUSIONS
Our data supports the notion that pretreatment of MSC with VPA and DFX improves the efficiency of MSC therapy by triggering homing regulatory signaling pathways.
Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran; Stem Cells and Regenerative Medicine Research Department, ACECR-Khorasan Razavi Branch, Mashhad, Iran.
Hamid Reza
HR
Bidkhori
Shahroud University of Medical Sciences, Shahroud, Iran.
Naghmeh
N
Ahmadiankia
Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran; Stem Cells and Regenerative Medicine Research Department, ACECR-Khorasan Razavi Branch, Mashhad, Iran.
Maryam Moghaddam
MM
Matin
Stem Cells and Regenerative Medicine Research Department, ACECR-Khorasan Razavi Branch, Mashhad, Iran.
Asieh
A
Heirani-Tabasi
Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran; Molecular Medicine Research Department, ACECR-Khorasan Razavi Branch, Mashhad, Iran.
Moein
M
Farshchian
Stem Cells and Regenerative Medicine Research Department, ACECR-Khorasan Razavi Branch, Mashhad, Iran.
Hojjat
H
Naderi-Meshkin
Stem Cells and Regenerative Medicine Research Department, ACECR-Khorasan Razavi Branch, Mashhad, Iran.
Mina
M
Shahriyari
Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran; Stem Cells and Regenerative Medicine Research Department, ACECR-Khorasan Razavi Branch, Mashhad, Iran.
Mahtab
M
Dastpak
Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran; Stem Cells and Regenerative Medicine Research Department, ACECR-Khorasan Razavi Branch, Mashhad, Iran; Cell and Molecular Biotechnology Research group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran.
Ahmad Reza
AR
Bahrami
CXCR4; CXCR7; Chemical treatment; CoCl2; Desferrioxamine; Homing; MSC; Valproic acid