Purpose: We have previously established a novel type of cells named MNCQQ cells which is from a serum free quantity and quality control culture (QQc) of peripheral blood mononuclear cells (MNCs) that increases the vasculogenic and tissue regeneration ability of MNCs. The medium derived from MNCQQ cells (QQ-Sup), has shown potential due to its rich composition in growth factors, cytokines, and exosomes, including numerous angiogenesis-related factors. Recently, emerging research on various cell-conditioned media has revealed significant therapeutic effects, prompting us to further investigate the specific therapeutic impact of QQ-Sup. This study aims to evaluate the angiogenic and regenerative capabilities of QQ-Sup on ischemic condition, assessing its potential in both in vitro and in vivo and exploring the molecular mechanisms behind its therapeutic properties.
Methods: QQ-Sup was collected from MNCQQ cultures and tested for its angiogenic potential on Human umbilical vein endothelial cells (HUVEC). The effects on HUVEC proliferation, migration, and tube formation were assessed through MTT assays, wound healing assays, and tube formation assays, respectively. Key angiogenesis-related factors in QQ-Sup were quantified using ELISA. Inhibition experiments using specific blockers validated the roles of these factors in angiogenesis. A hindlimb ischemia mouse model was also established to evaluate the therapeutic efficacy of QQ-Sup in vivo.
Results: QQ-Sup treatment significantly enhanced HUVEC proliferation (0.46 ± 0.09 vs. 0.84 ± 0.10/24h; p < 0.01), migration (29.21% ± 3.87% vs. 96.1% ± 3.21%/18h; p < 0.001), and tube formation (16.17 ± 3.16 vs. 22.29 ± 2.25/5h; p < 0.01). ELISA identified elevated levels of two key angiogenic factors in QQ-Sup, further confirmed by the reduced angiogenic activities upon their inhibition in functional assays. In vivo experiments showed that QQ-Sup-treated mice exhibited significantly better outcomes, with reduced ischemic damage.
Conclusion: This study confirms that QQ-Sup can significantly promote angiogenesis and accelerate wound healing through paracrine actions of key angiogenic factors, providing a promising therapeutic option for ischemic and vascular-related disorders in regenerative medicine.