Xiaozhen Dai

The role of CXCR7 on the adhesion, proliferation and angiogenesis of endothelial progenitor cells.

Previous studies confirmed that stromal cell‐derived factor 1 (SDF‐1) was a principal regulator of retention, migration and mobilization of haematopoietic stem cells and endothelial progenitor cells (EPCs) during steady‐state homeostasis and injury. CXC chemokine receptor 4 (CXCR4) has been considered as the unique receptor of SDF‐1 and as the only mediator of SDF‐1‐induced biological effects for many years. However, recent studies found that SDF‐1 could bind to not only CXCR4 but also CXC chemokine receptor 7 (CXCR7). The evidence that SDF‐1 binds to the CXCR7 raises a concern how to distinguish the potential contribution of the SDF‐1/CXCR7 pathway from SDF‐1/CXCR4 pathway in all the processes that were previously attributed to SDF‐1/CXCR4. In this study, the role of CXCR7 in EPCs was investigated in vitro. RT‐PCR, Western blot and flow cytometry assay demonstrate that both CXCR4 and CXCR7 were expressed highly in EPCs. The adhesion of EPCs induced by SDF‐1 was inhibited by blocking either CXCR4 or CXCR7 with their antibodies or antagonists. SDF‐1 regulated the migration of EPCs via CXCR4 but not CXCR7. However, the transendothelial migration of EPCs was inhibited by either blocking of CXCR4 or CXCR7. Both CXCR7 and CXCR4 are essential for the tube formation of EPCs induced by SDF‐1. These results suggested that both CXCR7 and CXCR4 are important for EPCs in response to SDF‐1, indicating that CXCR7 may be another potential target molecule for angiogenesis‐dependent diseases.

Chemokine receptor CXCR7 mediates human endothelial progenitor cells survival, angiogenesis, but not proliferation.

Stromal cell‐derived factor 1 (SDF‐1) is a critical regulator of endothelial progenitor cells (EPCs) mediated physiological and pathologic angiogenesis. It was considered to act via its unique receptor CXCR4 for a long time. CXCR7 is a second, recently identified receptor for SDF‐1, and its role in human EPCs is unclear. In present study, CXCR7 was found to be scarcely expressed on the surface of human EPCs derived from cord blood, but considerable intracellular CXCR7 was detected, which differs from that on EPCs derived from rat bone marrow. CXCR7 failed to support SDF‐1 induced human EPCs migration, proliferation, or nitric oxide (NO) production, but mediated human EPCs survival exclusively. Besides that, CXCR7 mediated EPCs tube formation along with CXCR4. Blocking CXCR7 with its antagonist CCX733 impaired SDF‐1/CXCR4 induced EPCs adhesion to active HUVECs and trans‐endothelial migration. Those results suggested that CXCR7 plays an important role in human cord blood derived EPCs in response to SDF‐1. J. Cell. Biochem. 113: 1437–1446, 2012.

Heparinized polyvinyl alcohol to specifically adsorb low-density lipoprotein from plasma

INTRODUCTION A medical adsorbent for blood purification was developed to specifically adsorb low-density lipoprotein (LDL) from hypercholesterolemia patients plasma by covalently immobilizing heparin onto the surface of polyvinyl alcohol (PVA) with the couplant toluence-2,4-diisocyanate (TDI). METHODS We used IR to demonstrate the success of covalently immobilizing heparin onto the surface, and investigated its adsorption of LDL, and primarily evaluated its hemo-compatibility using tests for platelet adhesion, the degree of platelet activation and a hemolysis test. RESULTS (1) Heparin was successfully covalently immobilized onto the surface, the maximum amount of heparin immobilized on the surface of 1g PVA-1799 granules was about 5 μg; (2) one optimal condition for adsorption of LDL from hyperlipidemia plasma was a pH within the range of 7.2∼9.5, accordingly the adsorptive ratio (adsorbent/g: plasma/L=1:2) for LDL was about 70%; (3) it exhibited good hemo-compatibility. CONCLUSION The adsorbent results in satisfactory adsorption of LDL with good hemo-compatibility; it could potentially be used as a blood purification material, and immobilization of heparin onto medical materials may be a way to develop an LDL-specific adsorbent for blood purification.

The Properties of a Compound Nerve Scaffold Based on Acellular-Matrix and Poly (lactide- Co-Glycolide)

With the development of tissue engineering for peripheral nerve regeneration, compound nerve scaffolds will be paid more attention in future. In this study, we attempted to fabricate a compound nerve scaffold with acellular pigskin and poly (lactide-co-glycolide) [PLGA] and characterized for its microstructure, in vitro degradation behaviour and biocompatibility. The microstructure of the scaffold was observed by Scanning electron microscope (SEM); Its in vitro degradation behaviour was evaluated by testing its max water absorption and ultimate mass loss; In vitro biocompatibility assessment was carried out to assess the morphology and viability of Schwann cells coculturing with the scaffold. According to the results, the scaffold was homogeneous and porous; its max water absorption was about 100.06 %, its ultimate mass loss was about 9.05% in PBS (pH = 7.4) during 8 weeks; SCs could adhere to the scaffold and MTT assay confirmed more adhesion of Schwann cells on the scaffold than its control. It could be concluded that this compound scaffold will be a potential artificial nerve scaffold.

Investigation on the Distribution and Expression of Caveolin-1 in Endothelial Cells under Disturbed Shear Stress by Vertical-Step Flow Chamber

Previous researches suggested that caveolae and Caveolin-1 (Cav-1) may regulate the vascular response to lamina shear stress alter. However, atherosclerosis (AS) preferentially affected at the outer edges of vessel bifurcations, where the flow patterns are disturbed. In this study, we fabricated a novel PDMS-based vertical-step flow chamber, which mimics the disturbed shear flow in AS preferential area of the artery to study the changes of Cav-1 in endothelial cell. Cells were seeded into the flow channel, and then exposed to disturbed shear stress (about 40 dynes/cm2) for 6 hours, 12 hours, 24 hours and 48 hours. It was found that in disturbed flow area, Cav-1 distribution shifted to the membrane from cytoplasm. In early stage of the stimulation, the expression of the Cav-1 decreased both on mRNA and protein level. The expression of Cav-1 in EC showed a significant decrease about 40% after exposure to shear stress for 48 hours. It suggests that disturbed shear stress can affect the distribution and expression of caveolin-1 in endothelial cell, which might play an important role in transducing mechanical stimuli into intracellular signals to causes ECs pathological changes and finally it might deduce into atheromatosis process.