To investigate the effects and underlying mechanism of CXC chemokine ligand-12 （CXCL12） pretreated bone marrow mesenchymal stem cells （BMSCs） on the wound healing of full-thickness skin defects in mice.

The 3^rd to 5^th passages of BMSCs were divided into control group， CXCL12 group， CXCL12 + CXCL12 receptor antagonist group and treated accordingly. After 48 h of culture， the cell survival rate was detected by cell counting kit 8 （CCK-8） method， and the cell proliferation activity was observed by staining with 5-ethynyl-2'-deoxyuridine （EdU） cell proliferation test kit. After 24 h of culture， the protein expressions of exchange protein directly activated by cAMP 1 （Epac1）， extracellular regulated protein kinase （Erk）， phosphorylated Erk （p-Erk） were detected by Western blotting， and the ratio of p-Erk to Erk was calculated. The number of samples in above experiments was six. Eighteen adult male BALB/c mice were divided into PBS group， BMSCs group and CXCL12 pretreated BMSCs group （6 mice in each group） according to the random number table method. Full-thickness skin defect wound model was created on the back of all mice. On day 3 post-wounding， the mice in PBS group， BMSCs group and CXCL12 pretreated BMSCs group were topically， intra-dermally administered 100 μl of PBS， 100 μl of cell suspension containing 1×10⁶ BMSCs and 100 μl of cell suspension containing 1×10⁶ CXCL12 pretreated BMSCs， respectively. On day 4， 7 and 10 post-wounding， the wound healing was observed and the wound healing rate was calculated. On day 11 post-wounding， the samples of wound tissue from 3 groups of mice were collected. Hematoxylin-eosin staining and Masson staining were used to detect the length of wound tissue defect and the collagen volume fraction （CVF）， respectively.

After 48 h of culture， compared with control group， the cell survival rate of CXCL12 group was significantly increased （P<0.05）. Compared with CXCL12 group， the cell survival rate of CXCL12 + CXCL12 receptor antagonist group was significantly decreased （P<0.05）. After 48 h of culture， the number of EdU-positive cells was increased， and the cell proliferation activity was enhanced in CXCL12 group compared to those in control group. In CXCL12 + CXCL12 receptor antagonist group， the number of EdU-positive cells was decreased and the cell proliferation activity was attenuated compared to those in CXCL12 group. After 24 h of culture， compared with control group， the protein level of Epac1 and the ratio of p-Erk to Erk in CXCL12 group were significantly increased （P<0.05）. Compared with CXCL12 group， the protein level of Epac1 and the ratio of p-Erk to Erk in CXCL12 + CXCL12 receptor antagonist group were significantly decreased （P<0.05）. On day 4， 7 and 10 post-wounding， the wound healing rate of mice in CXCL12 pretreated BMSCs group （56.7%±2.6%，70.4%±1.6%，84.5%±0.5%，respectively） was significantly higher than that in BMSCs group （37.4%±5.2%，49.2%±3.7%，67.9%±1.1%，respectively），P<0.05. On day 11 post-wounding， the length of wound tissue defect in CXCL12 pretreated BMSCs group was significantly shorter than that in BMSCs group ［（1.79±0.05） mm vs. （2.20±0.15） mm，P<0.05）］. On day 11 post-wounding， the CVF of BMSCs group was significantly increased compared with PBS group （P<0.05）. Compared with BMSCs group， the CVF of CXCL12 pretreated BMSCs group was significantly decreased （P<0.05）.

Pretreatment of BMSCs with CXCL12 could significantly promote the wound healing of full-thickness skin defects in mice， and the mechanism may be ascribed to the activation of Epac1/Erk signaling pathway by CXCL12 in the improvement of BMSCs' biological function， which finally enhance the therapeutic effects of BMSCs on skin defect wounds.