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MSC (mesenchymal stromal cells) precision medicine marker combination for screening and target treatment of patients with ARDS (acute respiratory distress syndrome)

A technology for treating drugs and patients, applied in the field of MSC precision medicine marker combination, can solve problems such as adverse effects, achieve the effect of preventing harmful effects and enhancing clinical treatment effects

Inactive Publication Date: 2019-08-09
GUANGZHOU INST OF RESPIRATORY DISEASE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since the use of MSCs may also lead to adverse outcomes, great caution must be exercised when applying MSCs to the treatment of human ARDS

Method used

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  • MSC (mesenchymal stromal cells) precision medicine marker combination for screening and target treatment of patients with ARDS (acute respiratory distress syndrome)
  • MSC (mesenchymal stromal cells) precision medicine marker combination for screening and target treatment of patients with ARDS (acute respiratory distress syndrome)
  • MSC (mesenchymal stromal cells) precision medicine marker combination for screening and target treatment of patients with ARDS (acute respiratory distress syndrome)

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0134] Example 1 Construction of mouse lung injury model and its response to MSC administration

[0135] 1. Construction of mouse lung injury model

[0136] 1. Experimental method

[0137] Male C57BL / 6 mice of 14-16 weeks were anesthetized and intubated, then infused with HCl (1N, pH 1) or normal saline (NS) at 3ml / kg, and mechanically ventilated for 10 minutes to make the instilled liquid in the lungs evenly distributed within.

[0138] Mice were anesthetized 48 hours after instillation and reintubated for low-pressure (LP) or high-pressure (HP) mechanical ventilation, and mice that retained spontaneous breathing (SB) were used as controls.

[0139] A total of 6 groups of mouse models were obtained:

[0140] (1) HCl+SB;

[0141] (2) NS+SB;

[0142] (3) HCl+LP;

[0143] (4) NS+LP;

[0144] (5) HCl+HP;

[0145] (6) NS+HP.

[0146] The physiological and biochemical indicators and gene protein expression of the mouse model were detected.

[0147] 2. Experimental results...

Embodiment 2

[0169] The pulmonary microenvironment characterization factor of embodiment 2 human ARDS patient

[0170] 1. Experimental method

[0171] To further investigate the relevance of the findings observed in mice, key proteins were examined in the plasma of ARDS and cardiac patients within 48 hours of admission in the ICU or CCU.

[0172] 2. Experimental results

[0173] A proteomic pattern similar to that present in mouse models was observed in ARDS patients ( Figure 12 A), with very good consistency.

[0174] The total antioxidant capacity, IL-6 and fibronectin concentrations in the lung microenvironment of CCU and ARDS patients were used to make 3D scatter plots. The microenvironment in the lungs of CCU and ARDS patients has different characteristics, and the average area (yellow box) of the three factors in patients with mild ARDS is used as a reference range to screen out ARDS patients who are suitable for MSC treatment ( Figure 12 B). Therefore, understanding the lung ...

Embodiment 3

[0179] Administration of embodiment 3 genetically modified MSCs

[0180] 1. Experimental method

[0181] In order to overcome the adverse effects produced by MSCs and avoid harmful lung microenvironment (i.e. pro-fibrotic, procoagulant and pro-inflammatory), we will carry human hepatocyte growth factor (LV HGF ) or human interleukin-10 (LV IL-10 ) lentivirus transiently transformed MSC to obtain human hepatocyte growth factor (MSC HGF ) or human interleukin-10 (MSC IL-10 ) MSC.

[0182] carrying hIL-10 (MSC IL-10 ) or hHGF (MSC HGF ) MSCs were administered after HCl treatment for 48 hours, carrying a luciferase reporter gene (MSC Luc ) MSCs and PBS as controls.

[0183] Specific administration method: intratracheal cell administration (IT) is carried out first, followed by intravenous cell administration (IV) 15 minutes later.

[0184] The physiological and biochemical indicators and gene protein expression of BALF and lung tissue homogenate were detected.

[0185] 2....

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Abstract

The invention discloses a MSC (mesenchymal stromal cells) precision medicine marker combination for screening and target treatment of patients with ARDS (acute respiratory distress syndrome), which isparticularly used for identifying whether the MSC can be used as an intrapulmonary microenvironment biomarker combination for treating the ARDS. The marker combination is IL-6, fibronectin and the total antioxidant capacity of the intrapulmonary microenvironment. When the intrapulmonary microenvironment biomarker combination is applied to guide the MSC to perform individualized treatment on a patient with the ARDS, the treatment on the ARDS by the MSC is thus more targeted, the harmful fibrosis adverse effects possibly generated when the MSC is applied to a patient with non-adaptive ARDS canbe prevented and reduced, and the MSC clinical treatment effects are enhanced.

Description

technical field [0001] The invention relates to the technical field of clinical treatment of acute respiratory distress syndrome, and more specifically to the combination of markers for screening and target treatment of MSC precision medicine for ARDS patients. Background technique [0002] Acute respiratory distress syndrome (ARDS) is a life-threatening disease with a high mortality rate. Various factors such as pneumonia, aspiration and sepsis can induce ARDS. ARDS is characterized by acute onset, bilateral lung infiltrates, hypoxemia, and pulmonary edema. Can develop from exudative inflammation to proliferative to fibrotic phase. Most ARDS patients require mechanical ventilation as the basic way of life support. Ventilator-induced lung injury (VILI) is the result of "biological trauma" and is a serious complication associated with pulmonary fibrotic changes. Fibrosis and more severe complications occur in ARDS patients. associated with high mortality. At present, ther...

Claims

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Application Information

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IPC IPC(8): G01N33/68C12Q1/6883
CPCG01N33/6869G01N33/68C12Q1/6883G01N2333/5412G01N2333/4753
Inventor 张海波黎毅敏钟南山亚瑟·斯勒茨基
Owner GUANGZHOU INST OF RESPIRATORY DISEASE
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