Iron-Quercetin Complex Preconditioning Human Peripheral Blood Mononuclear Cells Accelerates Angiogenic and Wound Healing Efficacy

Abstract Background: Cells-based therapy is a highly promising treatment paradigm in ischemic disease due to its ability to repair tissues when implanted into a damaged site. These therapeutic effects have been involving a strong paracrine component resulting from the high levels of bioactive molecules they secrete in response to the local microenvironment. Therefore, the secreted therapeutic can be modulated by preconditioning the cells during in vitro culture. Herein, we investigated the potential use of magnetic resonance imaging (MRI) probes “Iron-Quercetin complex” or IronQ for preconditioning peripheral blood mononuclear cells (PBMCs) to expand proangiogenic cells and enhance their secreted therapeutic factors. Methods: PBMCs obtained from healthy donor blood were cultured in the presence of the Iron-Quercetin complex. Preconditioning-PBMCs differentiated cells were characterized by immunostaining. An enzyme-linked immunosorbent assay to describe the secreted cytokines. In vitro migration and tubular formation using human umbilical vein endothelial cells (HUVECs) were completed to investigate the proangiogenic efficacy.Results: IronQ significantly increased mononuclear progenitor cells' proliferation and differentiation into the spindle-shape-like cells, expressing both hematopoietic and stromal cell markers. The expansion increased the number of colony-forming units (CFU-Hill). The conditioned medium obtained from IronQ-treated PBMCs contained a high level of Interleukin (IL)-8, IL-10, urokinase-type-plasminogen-activator (uPA), matrix metalloproteinases-9 (MMP-9), and tumor necrosis factor-alpha (TNF-α), and augmented migration and capillary network formation of HUVEC and fibroblast cells in vitro.Conclusions: Our study demonstrated that the IronQ-precondition PBMCs protocol could enhance the angiogenic and reparative potential of non-mobilized PBMCs. This protocol can be used as an adjunctive strategy to improve cell therapy's efficacy of PBMCs for ischemic diseases and chronic wound.