报告一：Early Diagnosis and Mechanobiology for Vessel Restenosis

报告二：Stem Cell Differentiation and Regenerative Medicine by Mechanobiology-assisted Microenvironments

 

 

报告一内容摘要：

The stenosis usually occurs after 8-16 weeks of vein graft bypass surgery which is the most common failure for vascular reconstruction in coronary and dialysis patients. The damage of endothelium is believed to be the major factor for initiation of stenosis in vein graft. However, the underline mechanism and pathological progression of stenosis remain unclear. By replacing the common carotid artery with the external jugular vein in rats, the vein graft bypass surgery was created in current study. We established a 50 MHz high frequency ultrasound (HFU) system to monitor the dynamic changes in tissue structures and inflammatory responses in vivo at different time points after microsurgery. The echogenicity and Nakagami parameters were measured from ultrasonography. The ultrasonography demonstrated a gradually increase of echogenicity on the vessel wall of vein graft after surgery for 1, 2, and 3 weeks. The Nakagami images suggested heterogeneous tissue properties when vein graft undergo pathological progressions. The three dimensional vessel structures in different time points were reconstructed by HFU images. With the application of finite element model, the wall shear stress and flow patterns were predicted after computational simulation. The wall shear stress was increased at suture junction and then decreased in the vein graft after 1 week of surgery. To further correlate the acquired ultrasonic images with changes in vascular structure, the histological assessments were performed by the hematoxylin and eosin (H&E) staining and the immunohistochemistry (IHC) staining. Significant increase of neointima thickness was identified after vein graft bypass surgery for 3 weeks. The vascular structure and tissue composition from H&E staining also confirmed the scatterer finding of Nakagami parameters in the hyperplasic intima. The positive staining of deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay showed the cell apoptosis of venous endothelial cells in vein graft. The cyclooxygenase 2 (COX-2) and leukotriene B4 receptor 1 (BLT1) expression levels were assessed to distinguish the molecular mechanism of tissue inflammation between cyclooxygenase and leukotriene signaling pathways. The increase of COX-2 expressions in neointima hyperplasia suggested the triggering of inflammatory response in vein graft might through COX-2 pathway.

报告二内容摘要：

Microenvironmental cues can control the cell fate and stem cell differentiations. The environmental stimulation for culturing cells can be modulated by mechanical stimulations, surface modifications, or the Bio-Micro-Electro-Mechanical System (BioMEMS). Adipose-derived stem cells (ASCs), an alternative source of adult mesenchymal stromal cells, possess high plasticity and abundant autologous cells. The BioMEMS technique was used to create a well-defined co-culture platform for embedding the ASCs within three dimensional collagen gel and facilitating the adjacent kidney epithelial cells to form column-like epithelium with functionalized renal markers. Using chitosan-coated surface or under biomechanical shear stress stimuli, our group also demonstrated the ability to differentiate ASCs into either endothelial or neuronal lineages in these microenvironments. In the rats with sciatic nerve injury, the application of neural lineage cells into the chitosan-coated nerve conduit showed significantly improvements of nerve regeneration with increases of myelinated axons density and myelin thickness, gastrocnemius muscle weight and muscle fiber diameter, and gait functions. Synergistic contributions were discovered when combining the endothelial and neural lineage cells for cell-based therapy in hypoxic-ischemic (HI) brain injury. The HI injured rat pups were divided into different groups to receive the treatments for saline, ASCs, endothelial, neural, and combination of endothelial and neural lineage cells (E+N) via intra-peritoneum injection. Significant reduction of cerebral infarction, increase of neurons, and decrease of cell apoptosis were observed after injected various therapeutic cells. The cell in different lineages contribute to their specific structures in the neurovascular units of injured brain. The E+N treatment provided a comprehensive recovery in HI brain injury that lights on a new therapeutic approach in future regenerative medicine.

 

 

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