Adipose-derived mesenchymal stem cells (Ad-MSCs) have been designated as the promising agents for clinical applications for easy accessibility, multi-linage differentiation and immunomodulation capacity. Despite this, optimal cell delivery conditions have remained as a clinical challenge and improvement of stem cell homing to the target organs is being considered as a major strategy in cell therapy systemic injection. It has been shown that homing of mesenchymal stem cells are increased when treated with physical or chemical hypoxia-mimicking factors, however, efficiency of different agents remained to be determined. In this study, hypoxia-mimicking agents, including valproic acid (VPA), cobalt chloride (CoCl₂) and deferoxamine (DFX) were examined to determine whether they are able to activate signaling molecules involved in migration of Ad-MSCs in vitro. We report that Ad-MSCs treated by DFX resulted in a significantly enhanced mRNA expression of MAPK4 (associated with MAPK signaling pathway), INPP4B (associated with Inositol polyphosphate pathway), VEGF-A and VEGF-C (associated with cytokine–cytokine receptor pathways), IL-8 and its receptor, CXCR2 (associated with IL-8 signaling pathway). While the cells treated with VPA did not show such effects and CoCl₂ only upregulated VEGF-A and VEGF-C gene expression. Furthermore, results of wound-healing assays showed migration capacity of Ad-MSCs treated with DFX significantly increased 8 and 24 h of the treatment. This study provides credible evidence around DFX, which might be an effective drug for pharmacological preconditioning of Ad-MSCs to boost their homing capacity and regeneration of damaged tissues though, activation of the migration-related signaling pathways.

脂肪来源的间充质干细胞 (Ad-MSCs) 因其易于获取、多向分化和免疫调节能力而被指定为临床应用的有前途的药物。尽管如此，最佳细胞递送条件仍然是一项临床挑战，改善干细胞归巢到靶器官被认为是细胞治疗全身注射的主要策略。已经表明，当用物理或化学缺氧模拟因子处理时，间充质干细胞的归巢会增加，但是，不同药剂的效率仍有待确定。在本研究中，缺氧模拟剂，包括丙戊酸 (VPA)、氯化钴 (CoCl ₂) 和去铁胺 (DFX) 以确定它们是否能够激活参与体外 Ad-MSC 迁移的信号分子。我们报告说，经 DFX 处理的 Ad-MSC 导致MAPK4（与 MAPK 信号通路相关）、INPP4B（与多磷酸肌醇通路相关）、VEGF-A和VEGF-C（与细胞因子-细胞因子受体通路相关）的mRNA 表达显着增强)、IL-8及其受体CXCR2（与 IL-8 信号通路相关）。而用 VPA 处理的细胞没有显示出这种作用，而 CoCl ₂仅上调了VEGF-A和VEGF-C基因表达。此外，伤口愈合试验的结果表明，用 DFX 处理的 Ad-MSCs 的迁移能力在处理 8 和 24 小时后显着增加。这项研究为 DFX 提供了可靠的证据，DFX 可能是一种有效的药物，可用于 Ad-MSCs 的药理预处理，以提高其归巢能力和受损组织的再生，激活迁移相关的信号通路。