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Microfluidic chip-based tumor brain metastasis model building method and use

A technology of microfluidic chip and brain metastasis, which is applied in the field of cell biology and tissue engineering, and can solve the problem that the method of tumor brain metastasis model has not yet appeared.

Inactive Publication Date: 2016-06-01
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the use of microfluidic chips to establish the simulation and bionic work of in vivo functional modules has gradually emerged, but the method of establishing an integrated blood-brain barrier structure and tumor brain metastasis model has not yet appeared.

Method used

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  • Microfluidic chip-based tumor brain metastasis model building method and use
  • Microfluidic chip-based tumor brain metastasis model building method and use
  • Microfluidic chip-based tumor brain metastasis model building method and use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Apply the primary extracted SD rat brain microvascular endothelial cells (ECs) and brain astrocytes (As), and use the self-designed and produced microfluidic chip to establish a high-throughput in vitro blood-brain barrier model, such as Figure 1-2 shown.

Embodiment 3

[0057] Using the microfluidic chip described in Example 1, a single blood-brain barrier model was constructed with endothelial cells and astrocytes, and then exogenous tumor cells A549, MDA- For single-cell suspensions of MB-231 and M624 cells, stand the whole chip sideways for 10 minutes with the two-dimensional channel on the top and the three-dimensional channel on the bottom. After all the cells are attached to the surface of the blood-brain barrier model, place the chip flat and continue to culture . Take pictures and collect data every 24 hours, and observe the number of cells and the moving distance of cells that tumor cells break through the blood-brain barrier and transfer into the side channel, such as Figure 4 , 5 shown. Depend on Figure 4 , 5 It can be seen that neither the single astrocyte model group nor the single endothelial cell model group can well play a barrier role against the invasion of exogenous tumor cells into the brain.

Embodiment 4

[0059] Endothelial cells and astrocytes were co-cultured with exogenous tumor cells, and after continuous culture for 48 hours, the data were collected by taking pictures to observe the growth, proliferation and sphere formation among cells, as shown in Figure 6 shown. Depend on Figure 6 It can be seen that neither endothelial cells nor astrocytes can co-grow and proliferate with exogenous tumor cells, that is, they cannot coexist, indicating that endothelial cells and astrocytes cannot co-exist with exogenous tumor cells. The interaction explains why the blood-brain barrier has no barrier effect on exogenous tumor cells.

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Abstract

The invention provides a microfluidic chip-based tumor brain metastasis model building method and use and belongs to the technical field of cytobiology and tissue engineering. The microfluidic chip comprises a waste liquid outlet, a cell inlet and a collagen inlet. The waste liquid outlet is communicated with the cell inlet through a two-dimensional passage. The collagen inlet is communicated with a three-dimensional passage. The junction of the two-dimensional passage and the three-dimensional passage forms a two dimensional-three dimensional microenvironment interface. The brain metastasis model building method utilizes the microfluidic chip and comprises 1, building a blood-brain barrier model through collagen perfusion into the chip and cell perfusion and culture on the chip, and 2, building a tumor brain metastasis model which is used for research on intracerebral metastasis of exogenous tumor cells and has characteristics of high throughput and high integrated level.

Description

technical field [0001] The invention belongs to methods of cell biology and tissue engineering, in particular to a method for establishing a model of tumor brain metastasis based on a microfluidic chip and its application. Background technique [0002] Tumor brain metastasis refers to the metastasis of tumors originating in other parts of the brain to the brain, also known as intracranial metastases, and its incidence rate accounts for 10%-15% of brain tumors. %. Clinical data show that brain metastasis of lung cancer is the most common, followed by breast cancer, melanoma, etc., and brain metastasis of tumors can occur to varying degrees. Although the incidence rate of intracranial metastases is lower than that of liver cancer and lung cancer, its clinical manifestations are more serious, mostly occurring in the late or late stage of tumors, and the mortality rate is relatively high. In recent years, the diagnosis and treatment of intracranial metastases have been gradual...

Claims

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Application Information

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IPC IPC(8): C12M3/00C12N5/071C12Q1/02
Inventor 秦建华许慧李中玉
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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