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Application of oltipraz in reversal of senescence-like phenotype of Hutchinson-Gilford progeria syndrome

A technology of progeria and oltipraz applied in the field of biomedicine

Active Publication Date: 2016-07-20
INSITUTE OF BIOPHYSICS CHINESE ACADEMY OF SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are no in vitro and in vivo studies on the use of small molecule compounds to effectively improve the aging phenotype of adult stem cells derived from HGPS patients
There is no report on the use of oltipraz in HGPS related studies

Method used

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  • Application of oltipraz in reversal of senescence-like phenotype of Hutchinson-Gilford progeria syndrome
  • Application of oltipraz in reversal of senescence-like phenotype of Hutchinson-Gilford progeria syndrome
  • Application of oltipraz in reversal of senescence-like phenotype of Hutchinson-Gilford progeria syndrome

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Embodiment 1, obtaining HGPS-MSC and the identification of aging phenotype thereof

[0060] 1. Culture of induced pluripotent stem cells derived from HGPS patients and differentiation of MSCs

[0061] In iPSCs derived from HGPS patients (HGPS-iPSCs), the LMNA gene has a mutation (LMNA genome sequence is GenBank: NG_008692.2; cDNA sequence is GenBank: NM_170707.3), and the mutation type is C1824T (GGCGG is mutated to GGTGG). The reference sequence of the site is the CDS region in LMNAcDNA sequence GenBank: NM_170707.3. In this example, HGPS-iPSCs were further differentiated into mesenchymal stem cells (HGPS-MSCs) in vitro. The specific method is as follows:

[0062] HGPS-iPSCs were differentiated into embryoid bodies (EBs) for 14 days. EBs were seeded in matrigel-coated 6-well plates and cultured for 2 weeks until fibrous cells appeared. After another passaging, the cell populations in which CD73, CD90 and CD105 were all positive were sorted by flow cytometry, which w...

Embodiment 2

[0085] Example 2. Using HGPS-MSC to screen small molecular compounds for anti-aging phenotypes

[0086] When the inventors of the present invention cultivated the HGPS-MSCs prepared in Example 1, they established a screening method for small molecular compounds targeting anti-aging phenotypes, and found that Oltipraz can reverse the aging phenotypes of HGPS-MSCs. details as follows:

[0087] HGPS-MSC cells were divided into 5×10 4 Each well was spread in a six-well plate, and the second day after the cells adhered to the wall, in the experimental group, 25 μM Oltipraz (Oltipraz) medium was added to continue culturing (while setting the HGPS-MSC without Oltipraz treatment cells as a control) were continuously cultured for 21 hours, during which three cell passages were experienced, and then the HGPS-MSCs and controls treated with the oltipraz (Oltipraz) were analyzed as follows:

[0088] (1) Senescence-associated β-galactosidase staining

[0089] The specific method is carri...

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PUM

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Abstract

The invention discloses application of oltipraz in reversal of senescence-like phenotype of Hutchinson-Gilford progeria syndrome (HGPS). The invention provides a new use (I) or (II) of oltipraz specifically as follows: (I) application in the preparation of a product for delaying or reversing the senescence-like phenotype of HGPS; (II) application in the delay or reversal of the senescence-like phenotype of HGPS. Experiments show that oltipraz can reduce the proportion of positive beta-galactosidase staining cells in HGPS-MSCs, increase the expression quantity of nuclear membrane-associated proteins LAP2 and / or LaminB1, and improve the survival ability of HGPS-MSCs in vivo, namely, oltipraz can improve the senescence-like phenotype of HGPS-MSCs and is important to delay or reverse the senescence-like phenotype of HGPS.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to a new application of oltipraz, in particular to the application of oltipraz in reversing the aging phenotype of progeria in human children. Background technique [0002] Aging is a process in which the human body gradually becomes disordered, and is considered to be the most influential pathogenic factor for various diseases such as tumors and cardiovascular diseases. The human body has a certain self-renewal ability, and this self-renewal ability is also strictly regulated. With the aging of the body, the self-regulating balance of stem cells is destroyed, and the regeneration ability of tissues and organs decreases, which leads to aging-related diseases. Therefore, stem cell senescence is currently considered to be one of the important causes of body aging, and how to delay or reverse stem cell senescence has become a research hotspot in the field of basic and translational research on...

Claims

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Application Information

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IPC IPC(8): A61K31/497A61P43/00
CPCA61K31/497
Inventor 刘光慧曲静张维琦任若通杨济平王丽霞
Owner INSITUTE OF BIOPHYSICS CHINESE ACADEMY OF SCIENCES
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