Chemically primed bone-marrow derived mesenchymal stem cells show enhanced expression of chemokine receptors contributed to their migration capability

Objective(s):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. Materials and Methods: BM-MSCs were treated at passage ۲ for our gene expression profiling. All qPCR experiments were performed by SYBR Green method in CFX-۹۶ 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), CoCl۲, and desferrioxamine (DFX) are described. Results show DFX efficiently up-regulate the CXCR۷ and CXCR۴ gene expression while VPA increase only the CXCR۷ gene expression and no significant change in expression level of CXCR۴ and the CXCR۷ gene was detectable by CoCl۲ treatment. Chemotaxis assay results show that pre-treatment with DFX, VPA, and Cocl۲ 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 Cocl۲ treatments. Conclusion: 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.

Keywords:

CXCR۴ , CXCR۷ , CoCl۲ , Desferrioxamine , MSC , Chemical treatment , Homing , Valproic acid