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Application of mesenchymal stem cells in preparing medicine for treating neurodegenerative diseases

A technology of neurodegenerative and mesenchymal stem cells, applied in the field of biomedicine

Pending Publication Date: 2016-11-23
SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although MSCs transplantation has achieved obvious therapeutic effects on PD, its specific mechanism of action needs further study.

Method used

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  • Application of mesenchymal stem cells in preparing medicine for treating neurodegenerative diseases
  • Application of mesenchymal stem cells in preparing medicine for treating neurodegenerative diseases
  • Application of mesenchymal stem cells in preparing medicine for treating neurodegenerative diseases

Examples

Experimental program
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Effect test

preparation example Construction

[0091] Preparation of MSCs derived from human umbilical cords: Umbilical cords were obtained from full-term healthy pregnant women. The umbilical cords were collected under aseptic conditions, stored on ice, and immediately sent to the laboratory for preparation. Adopt the tissue block adherent culture method, put the fresh umbilical cord into a large petri dish, and remove the amniotic membrane and blood vessels. Cut the separated umbilical cord to about 1mm with ophthalmic scissors 3 For tissue pieces of different sizes, put an appropriate amount into a sterile petri dish, covering 70% of the bottom area of ​​the petri dish, add medium and culture for 9-11 days, long spindle cells can be seen growing from the edge of the tissue piece, replace every 2 days The culture medium was changed once, and the medium was changed twice continuously. When the adherent cells reached 90% of the bottom of the bottle, they were digested and passaged, and the cells were identified.

[0092]...

Embodiment 1

[0131] Example 1. MSCs (Cytokine-primed MSCs, pMSCs) pretreated with inflammatory factors can significantly alleviate Parkinson's disease (PD) in mice

[0132] 1. Relief effect of pMSCs cell transplantation on PD disease in mice

[0133] Preparation of MSCs pretreated with proinflammatory factors (IFN-γ+TNF-α): Add IFN-γ at a final concentration of 10ng / ml and TNF-α at a final concentration of 10ng / ml to the MSCs medium and treat for 12-24 hours , to obtain MSCs pretreated with proinflammatory factors, namely pMSCs.

[0134] In order to simulate the influence of the immune environment on MSCs in vivo, the method of pretreatment of cells with pro-inflammatory factors in vitro is proposed, and the experiment is carried out in a situation close to the actual situation of in vivo treatment. One week after PD mice were injected with 6-OHDA striatum, the ipsilateral striatum was injected with human umbilical cord-derived MSCs (the injection volume was 5×10 4 cells / only), and PBS w...

Embodiment 2

[0146] Example 2, Effects of MSCs Pretreated by Inflammatory Factors on Oxidative Stress in PD Mice

[0147] 1. pMSCs transplantation significantly reduces the oxidative stress response in the striatal region of the brain tissue of PD mice

[0148] In order to detect the influence of pMSCs (preparation method is the same as in Example 1) on the level of oxidative stress in the brain tissue area of ​​PD mice, the present inventors extracted tissue samples of the brain striatum of the PD mice of the control group and the treatment group, and detected in the samples Total free radicals include levels of ROS, RNS, etc.

[0149] It was found that after injection of 6-OHDA, the level of ROS / RNS in the striatum region of the mouse brain was significantly increased, and when transplanted into pMSCs, the level of ROS / RNS returned to the normal mouse level ( Figure 4 a). Equally, the inventor has also detected the content of nitric oxide (NO) in each group of samples, and the result ...

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Abstract

The invention relates to application of mesenchymal stem cells in preparing medicine for treating neurodegenerative diseases. It is revealed for the first time that the relieving effect of mesenchymal stem cells on neurodegenerative diseases can be significantly promoted after mesenchymal stem cells are treated with inflammatory factors. The invention further provides a pharmaceutical composition containing the cells. The invention further discloses the key role of indoleamine 2,3-dioxygenase in treating neurodegenerative diseases with mesenchymal stem cells.

Description

technical field [0001] The invention belongs to the field of biomedicine, and more specifically, the invention relates to the application of mesenchymal stem cells in the preparation of drugs for treating neurodegenerative diseases. Background technique [0002] Parkinson's disease and Parkinson's syndrome (parkinson disease, PD) is a common neurodegenerative disease, and its characteristic pathological change is the progressive loss of dopamine (DA) neurons in the substantia nigra of the midbrain. This in turn leads to a decrease in dopamine neurotransmitters projecting to the striatum. Genetic factors, environmental factors, aging, oxidative stress, and inflammation are all involved in the degeneration and death process of dopaminergic neurons in Parkinson's disease. Among them, oxidative stress plays a dominant role in various neurodegenerative mechanisms and plays an important role in the death of dopamine neurons. At present, there is still no effective treatment for ...

Claims

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Application Information

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IPC IPC(8): C12N5/0775A61K35/28A61P25/28A61P25/16
Inventor 时玉舫曹巍王莹
Owner SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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