Construction method of cerebral cavernous hemangioma cell model and application of cell model in new drug screening

Abstract

The invention discloses a construction method of a cerebral cavernous hemangioma cell model. The construction method comprises the following steps: inoculating vascular endothelial cells transfected with CCM3 gene siRNA onto fibroblasts fused in monolayer, and carrying out co-culture; or coating the vascular endothelial cells transfected with CCM3 gene siRNA on microcarrier ball beads, then embedding the microcarrier ball beads into fibrin glue, then laying the fibroblasts at the upper layer of the fibrin glue, and carrying out co-culture. The cell model has phenotypes in increase of budding vascular endothelial cells, expansion of lumen formation and reduction of pericyte recruitment, accords with pathological characteristics of human cerebral cavernous hemangioma, is especially applicable to study of human cerebral cavernous vascular malformation pathogenesis and development of a corresponding therapeutic drug and also can be applied to screening of drugs, pharmaceutical effect observation and pharmaceutical effect evaluation.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a method for constructing a cerebral cavernous hemangioma cell model and its application in new drug screening. Background technique [0002] Cerebral carvernous malformation (CCM) is a kind of vascular malformation that occurs in the central nervous system. The disease rate is about 0.1% to 4%. [0003] CCM is composed of cavernous sinuses of various sizes lacking muscular layer and elastic fibers, clusters of telangiectasia, and the inner wall is a single layer of flattened endothelial cells (ECs), lacking pericyte (PCs) coverage, There is no normal vascular basement membrane. Changes in the vascular endothelial barrier lead to increased vascular permeability, red blood cell extravasation, and secondary brain parenchymal inflammation, which significantly increases the risk of stroke, epilepsy, and neurological deficit. [0004] CCM is divided into sporadic an...

AI Technical Summary

Problems solved by technology

Currently, drug screening methods mainly include in vivo and in vitro screening methods. In vivo screening methods are costly and difficult to operate, which is not conducive to high-throughput drug screening; in vitro screening methods are mainly realized at the molecular and cellular levels, and have the advantages of materials. Small amount, clear mechanism of action, easy to use in large-scale screening, etc., is the main method of drug screening

However, there is no recognized CCM cell model at present. Therefore, it is necessary to establish a CCM cell model to accelerate the development of CCM drugs.

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