title: CXCR-7 receptor promotes SDF-1α-induced migration of bone marrow mesenchymal stem cells in the transient cerebral ischemia/reperfusion rat hippocampus.
abstract: The stromal cell-derived factor 1/C-X-C chemokine receptor type 4 (SDF-1/CXCR-4) axis plays an important role during stem cell recruitment. SDF-1 can also bind the more recently described CXCR-7 receptor, but effects of SDF-1/CXCR-7 signaling on stem cell migrating to ischemic brain injury area are little known. In the present study, we investigated the effect of CXCR-7 on bone marrow mesenchymal stem cell (BMSC) migration toward SDF-1α in the cerebral ischemia/reperfusion (I/R) rat hippocampus. We cultured BMSCs from rats and characterized them using flow cytometry, immunocytochemistry, western blotting, and immunofluorescence to detect SDF-1α, CXCR-4, and CXCR-7 expression in third passage BMSCs (P3-BMSCs). We also prepared the model of transient cerebral I/R by four-vessel occlusion (4-VO), and BMSCs were transplanted into I/R rat brain via lateral ventricle (LV) injection (20μl, 1×10(6)/ml). After that, we examined the effect of BMSCs migration in the cerebral I/R rat hippocampus through Transwell chamber assay. Our results show that SDF-1α, CXCR-4, and CXCR-7 were expressed in P3-BMSCs. Moreover, SDF-1α expression was increased in I/R hippocampus. At 48h after transplant, green fluorescent BrdU-BMSCs were observed in transplant groups, but no green fluorescent BrdU-BMSCs were seen in medium group. Among BMSCs transplant groups, the number of BrdU-BMSCs positive cell was the highest in BMSC group. Treatment with AMD3100 and/or CXCR-7 neutralizing antibody decreased the number of BMSC migration. Collectively, these findings indicate that CXCR-4 and -7 receptors were co-expressed in BMSCs and synergistically promoted BMSC migration. The effect of CXCR-7 was stronger than that of CXCR-4. Moreover, BMSCs that migrated to hippocampus promoted the autocrine and paracrine signaling of SDF-1α.
authors.affiliation: Department of Human Anatomy and Neurobiology, Xuzhou Medical College, No. 209 Tong-shan Road, Jiangsu, Xuzhou 221004, China. Electronic address: ylwang-xz@163.com.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221004, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fu
authors.affiliation: Department of Human Anatomy and Neurobiology, Xuzhou Medical College, No. 209 Tong-shan Road, Jiangsu, Xuzhou 221004, China.
authors.forename: Shichun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Human Anatomy and Neurobiology, Xuzhou Medical College, No. 209 Tong-shan Road, Jiangsu, Xuzhou 221004, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Human Anatomy and Neurobiology, Xuzhou Medical College, No. 209 Tong-shan Road, Jiangsu, Xuzhou 221004, China.
authors.forename: Zhi'an
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Human Anatomy and Neurobiology, Xuzhou Medical College, No. 209 Tong-shan Road, Jiangsu, Xuzhou 221004, China.
authors.forename: Diansuai
authors.initials: D
authors.lastname: Gao
authors.affiliation: Department of Human Anatomy and Neurobiology, Xuzhou Medical College, No. 209 Tong-shan Road, Jiangsu, Xuzhou 221004, China.
authors.forename: Tiejun
authors.initials: T
authors.lastname: Xu
mesh_terms: D000818:Animals; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054387:Receptors, CXCR / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: C501898:Ackr3 protein, rat; C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D054387:Receptors, CXCR; D019718:Receptors, CXCR4
keywords: Bone marrow mesenchymal stem cell; C-X-C chemokine receptor 7; Hippocampus; Ischemia/reperfusion; Migration; Stromal cell-derived factor-1α