Yu Jiao-Le, Deng Ruixia, Chung Sookja K, Chan Godfrey Chi-Fung
Department of Pediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong Special Administration Region, People's Republic of China.
Beijing Children's Hospital, Capital Medical University, Beijing, People's Republic of China.
Stem Cells. 2016 Apr;34(4):948-59. doi: 10.1002/stem.2264. Epub 2016 Jan 4.
How to enhance the homing of human mesenchymal stem cells (hMSCs) to the target tissues remains a clinical challenge nowadays. To overcome this barrier, the mechanism responsible for the hMSCs migration and engraftment has to be defined. Currently, the exact mechanism involved in migration and adhesion of hMSCs remains unknown. Exchange protein directly activated by cAMP (Epac), a novel protein discovered in cAMP signaling pathway, may have a potential role in regulating cells adhesion and migration by triggering the downstream Rap family signaling cascades. However, the exact role of Epac in cells homing is elusive. Our study evaluated the role of Epac in the homing of hMSCs. We confirmed that hMSCs expressed functional Epac and its activation enhanced the migration and adhesion of hMSCs significantly. The Epac activation was further found to be contributed directly to the chemotactic responses induced by stromal cell derived factor-1 (SDF-1) which is a known chemokine in regulating hMSCs homing. These findings suggested Epac is connected to the SDF-1 signaling cascades. In conclusion, our study revealed that Epac plays a role in hMSCs homing by promoting adhesion and migration. Appropriate manipulation of Epac may enhance the homing of hMSCs and facilitate their future clinical applications.
如何增强人间充质干细胞（hMSCs）向靶组织的归巢能力，至今仍是一项临床挑战。为克服这一障碍，必须明确hMSCs迁移和植入的机制。目前，hMSCs迁移和黏附的确切机制仍不清楚。环磷酸腺苷直接激活的交换蛋白（Epac）是在环磷酸腺苷信号通路中发现的一种新蛋白，可能通过触发下游Rap家族信号级联反应，在调节细胞黏附和迁移方面发挥潜在作用。然而，Epac在细胞归巢中的具体作用尚不清楚。我们的研究评估了Epac在hMSCs归巢中的作用。我们证实hMSCs表达功能性Epac，其激活显著增强了hMSCs的迁移和黏附能力。进一步发现，Epac的激活直接促进了基质细胞衍生因子-1（SDF-1）诱导的趋化反应，SDF-1是一种已知的调节hMSCs归巢的趋化因子。这些发现表明Epac与SDF-1信号级联有关。总之，我们的研究表明Epac通过促进黏附和迁移在hMSCs归巢中发挥作用。对Epac进行适当调控可能会增强hMSCs的归巢能力，并促进其未来的临床应用。
