Application Of Hypertrophic Chondrocytes And Sodium Alginate Complex In The Embolization Treatment Of Arteriovenous Malformation

AVM(arteriovenous malformation, AVM) is a common congenital vascular abnormalities, arteriovenous directly connected, during which no capillaries, leading to a series of hemodynamic disorders. Common in young adults aged 20 to 40. Currently,main treatments for arteriovenous malformation include surgery, radiation therapy and intravascular interventional therapy. With the development and progress of science and technology, in recent years, endovascular treatment due to have the remarkable characteristic of small trauma, got rapid development. Endovascular embolization gradually become the main means for the treatment of AVM owing to the endovascular embolization material continuously development and research.However,the embolizaion material constraints the therapeutic effect of embolization treatment embolization materials at home and abroad mainly includes three types: particles embolizaion materials, adhesive embolizaion materials and nonadhesive embolization materials, these three kinds of embolizaion materials respectively has its disadvantages. Alginate is a natural polysaccharide extracted from seaweed, it has good solubility in water,after when it comes in contact with a divalent calcium ion to form a gel having a certain intensity.It has good biocompatibility, but also has good dispersivity, over time, gradually degraded to nontoxic polysaccharide excreted in the urine.Because alginate gel is biodegradable, so it can not guarantee a permanent embolization effect, we have to turned to focus on cells and alginate gel combination.Alginate gel degrade while cell propagate, thus ensuring the long-term possibility of embolizaion effect. At present the main source for cells are fibroblast and bone marrow mesenchymal stem cells: fibroblast were abundant in origin and strong in proliferation, but it has poor ability to secrete matrix, so it is not conducive to cell survival; mesenchymal stem cells have multiple differentiation potential and good self-renewal capacity, but owing to its less content,it can not be used. Chondrocytes is the only cell in cartilage tissue, which have a certain mechanical strength to secrete large amounts of matrix components, while under hypoxic conditions can survive.Hypertrophy is a key endochondral ossification physiological steps calcifications hypertrophic cartilage cells gradually ossification may further increase the strength of the cell, while hypertrophic cartilage may secrete growth factors such as VEGF, promote cell proliferation and growth. Therefore, the present study, hypertrophic chondrocytes and alginate gel was choosed to form a complex, as the treatment of arteriovenous malformation embolization material. In this experiment, rabbit cartilage cells in primary culture was used to obtain the most suitable experimental cell passages, while the cells of each signature gene hypertrophy treatment were identified. The optimum concentration of sodium alginate and Ca Cl2 was obtained through experiments and literature, then the hypertrophy of chondrocytes gel mixed with alginate, alginate gel to give the cell complex, in vitro cell viability for 1 month. After the alginate gel- cell complexes transplanted into nude mice analysis alginate gel- biocompatibility complex. Finally, the cell mixture of sodium alginate and Ca Cl2 by double catheter into the experimental model validation seaweed gel- cell complex treatment of arteriovenous malformation feasibility of endovascular embolization material as. The results showed:1.The primary chondrocytes was isolated successfully, according to the survival curve of different passages of cells, the 3rd passage cells was selected as the cell source.2.After the hypertrophic treatment of 3rd passage cells, the collagen type Ⅱcontent basically unchanged. Hypertrophy of chondrocytes marker gene type collagen X began to appear, and gradually increase along with the process of hypertrophy, extracellular matrix secretion increase.3.The optimal concentration ratio of sodium alginate and Ca Cl2 was selected, and the cells were transplanted into the alginate gel, the cells were in good condition and showed good cell viability.4.Alginate-cell compound were transplanted to nude mice for one month,material analysis, alginate gel volume reminded unchanged,while there was no obvious inflammatory phenomena in nude mice in vivo, indicating good biocompatibility.5.A renal artery embolization model was prepared, mixture of sodium alginate-cells into a rabbit renal artery with Ca Cl2 while successful embolization of the right artery. Ultrasound and MRI showed that after two months of embolization, obvious blood flow was not found,at the same time with obvious astrophy of the right kidney.The above findings provide a preliminary experimental reference for the further exploration of the embolization material of arteriovenous malformation.