CN111281885A

CN111281885A - Method for reversing liver fibrosis by applying stem cell therapy

Info

Publication number: CN111281885A
Application number: CN202010095337.0A
Authority: CN
Inventors: 李军
Original assignee: Car T Shanghai Biotechnology Co ltd
Current assignee: Car T Shanghai Biotechnology Co ltd
Priority date: 2020-02-17
Filing date: 2020-02-17
Publication date: 2020-06-16

Abstract

The invention discloses a method for reversing hepatic fibrosis by applying stem cell therapy, which comprises the steps of firstly extracting autologous adipose-derived stem cells from a liver disease patient, then transporting the autologous adipose-derived stem cells to a GMP laboratory, and separating and obtaining initial autologous adipose-derived stem cells in the GMP laboratory; culturing, amplifying and purifying the initial autologous adipose-derived stem cells under appropriate conditions to obtain seed autologous adipose-derived stem cells, and freezing; and finally, transporting the amplified seed autologous adipose-derived stem cells to a hospital through a cold chain, and infusing the autologous adipose-derived stem cells back to the body of the liver disease patient in the hospital in an intravenous injection mode. The stem cell therapy of the invention can remarkably reverse liver fibrosis of patients with liver diseases, can bring new hope for treatment of the patients with liver diseases, can effectively recover liver functions, makes reversal of liver cirrhosis possible, improves life quality of the patients with liver cirrhosis, prolongs life of the patients with liver cirrhosis, can recover liver functions of the patients with liver diseases at the end stage, and can be safely used with reassurance.

Description

Method for reversing liver fibrosis by applying stem cell therapy

Technical Field

The invention belongs to the technical field of cell therapy, and particularly relates to a method for reversing hepatic fibrosis by applying stem cell therapy.

Background

Data published by the association of Chinese physicians show that by the end of 2010, the incidence rate of the total nonalcoholic fatty liver in China is about 15%, the incidence rate of fatty liver in first-line cities is up to 20% -30% in advanced countries in the west, and the incidence rate of fatty liver in severely obese people is up to 61% -94%. According to the calculation, at least 2 hundred million people have fatty liver disease in China at present, and the number of people who are converted into hepatic fibrosis and hepatic cirrhosis from the fatty liver disease people is about 400-800 ten thousand in the future. The progression of liver disease is: healthy liver, hepatic fibrosis, liver cirrhosis, and liver cancer. Hepatic fibrosis is the essential stage for the development of chronic diseases such as chronic hepatitis, fatty liver, alcoholic liver and the like to cirrhosis. The proportion of hepatic fibrosis of patients with mild and moderate hepatitis is 64% and 100%, respectively. The etiology of the hepatic fibrosis is diversified, the treatment is complex, and the progress of the hepatic fibrosis can be effectively slowed down or even reversed by aiming at the etiology treatment. Hepatic fibrosis is a pathophysiological process, which refers to a pathological process in which connective tissues in the liver abnormally proliferate due to various pathogenic factors, resulting in excessive precipitation of diffuse extracellular matrix in the liver. Any liver injury has the process of hepatic fibrosis in the process of liver repair and healing, and if the injury factor cannot be removed for a long time, the process of fibrosis can be continuously developed into cirrhosis for a long time, so that the liver fibrosis is not an independent disease, and a plurality of chronic liver diseases can cause hepatic fibrosis.

The causes of hepatic fibrosis are roughly classified into infectious, congenital and chemical metabolic defects, autoimmune hepatitis, primary hepatic cirrhosis, primary sclerosing cholangitis, and the like. In general, chronic liver diseases are often accompanied by hepatic fibrosis due to continuous liver damage. The chronic hepatitis B is the most and the chronic hepatitis C is not rare in the chronic liver diseases in China. Both hepatitis types stimulate the immune system of human body due to the replication of hepatitis virus, so that when immune lymphocytes clear the virus, liver cells are accidentally injured, inflammation in the liver is generated, and fibrous tissue hyperplasia is induced, thus hepatic fibrosis is caused. With the improvement of the living standard of people, the incidence of alcoholic liver diseases and non-alcoholic liver diseases in China is continuously increased. The more serious of these two liver diseases is steatohepatitis, and if not actively treated, the damaged liver cells can also stimulate massive proliferation of fibrous tissues in the liver, progressing from liver fibrosis to cirrhosis. Some drug-induced liver diseases, metabolic liver diseases, autoimmune liver diseases or schistosomiasis and the like are also infected with liver fibrosis. Because the constitutional conditions and the pathological conditions of each patient are different, the degree of hepatic fibrosis and the degree of disease condition or the length of disease course may not be in direct proportion. Liver fibrosis is a great hazard, so the best treatment time needs to be grasped. It is critical that patients with chronic liver disease prevent hepatic fibrosis in advance, and do not think about a policy before hepatic fibrosis is actively brought to the home.

There are many causes of hepatic fibrosis, and viral hepatitis, alcoholic liver, fatty liver, autoimmune diseases, etc. are more common clinically. Strictly speaking, liver fibrosis does not have any clinical symptoms, mainly the clinical symptoms of hepatitis caused by damage to the liver by various factors or the further aggravation of the liver cirrhosis, and the main manifestations of liver fibrosis are as follows: fatigue, weakness, anorexia, nausea, vomiting, chronic dyspepsia, abdominal distention, constipation or diarrhea, dull pain in the liver, etc. Clinically, some patients have no obvious history of chronic liver diseases and can find the chronic liver diseases through further examination. Many patients with chronic hepatitis have symptoms of acid regurgitation, belching, hiccup, vague pain in the upper abdomen and distention in the upper abdomen. Chronic hepatitis affects the synthesis of prothrombin and other coagulation factors due to reduced liver function. The clinical manifestations of hepatic fibrosis are spider nevus, epistaxis, gingival bleeding, skin and mucous membrane with purpura or bleeding spots, and women often have menorrhagia. The bleeding symptoms mentioned above often appear to indicate that liver fibers have progressed to the stage of cirrhosis.

The pathological causes of liver fibrosis are that 1, liver damage can cause a large amount of lipid peroxidation products to overflow in the occurrence and development process of liver fibrosis, and can generate cytokines such as Transforming Growth Factor (TGF) and the like at the same time of activating HSC, functional basement membranes (IV type collagen and LN) under normal liver blood sinus endothelium play an important role in maintaining HSC in a static state, once the basement membranes are damaged, the HSC is activated and converted into Myofibroblast (MFB), and express a large amount of muscular skeleton proteins such as smooth muscle actin (α -SMA) play an important role, the activation of the HSC is a central link of liver fibrosis occurrence, and the blood sinus endothelial cells, liver cells Kupffer cells and the HSC are all involved in liver fibrosis formation under the action of initiation factors such as liver cell damage, necrosis and the like, and particularly the initiation activation of the Kupffer cells plays an important role in the initiation of ECM generation.

The method for preventing hepatic fibrosis comprises the following steps: 1. and (3) mood stabilization: the liver is closely related to mental emotion, so that bad emotion, mental depression, rage and agitation all affect the function of liver and accelerate the development of pathological changes. 2. Active treatment of liver inflammation: liver injury is caused by various factors, liver protection and anti-inflammatory treatment are important in the inflammatory activity period, hospitalization is needed if necessary, and the patients are careless because of mild symptoms or no symptoms, so that inflammation is controlled in the shortest time, and liver fibrosis is avoided. 3. The medicine is simple to use: blindly abusing general drugs can increase liver burden and is not conducive to liver recovery. 4. Smoking cessation and wine avoiding: long-term drinking, especially hard liquor, can lead to alcoholic cirrhosis. 5. Dynamic and static combination: the liver fibrosis has a compensatory decline and is absolutely bedridden for rest when ascites or infection occurs. Can do some easy work or proper activities in the period of the vigorous compensation function and stable state of illness, and perform beneficial physical exercise. 6. And (3) diet conditioning: the diet is low in fat, high in protein and vitamins and easy to digest, and timing, quantitative and moderate effects are achieved. Attention is paid to the prevention and treatment of various primary diseases, the active prevention and treatment of chronic hepatitis, schistosomiasis and gastrointestinal infection, the contact and the application of toxic substances to the liver are avoided, and pathogenic factors are reduced. The prior art treatment method for resisting hepatic fibrosis mainly comprises the following steps: removing pathogenic factors aiming at the primary disease, such as anti-hepatitis B and hepatitis C virus therapy, anti-schistosomiasis therapy, alcohol withdrawal and the like. The treatment aiming at the hepatic fibrosis is carried out, for example, by inhibiting inflammation or lipid peroxidation, or inhibiting the proliferation and activation of hepatic stellate cells, promoting the degradation of collagen and the like.

Disclosure of Invention

The invention provides a method for reversing hepatic fibrosis by applying stem cell therapy to overcome the defects in the prior art.

The invention is realized by the following technical scheme: a method for reversing liver fibrosis by applying stem cell therapy specifically comprises the following steps: firstly, autologous adipose-derived stem cells are extracted from the body of a patient with liver disease, and then the autologous adipose-derived stem cells are culturedTransporting the cells to a GMP laboratory under the condition of bacteria and cold chain, wherein the GMP laboratory adopts a biological laboratory which meets the standard of the international cell preparation quality management system, and separating and obtaining the starting autologous adipose-derived stem cells in the GMP laboratory; culturing, amplifying and purifying the initial autologous adipose-derived stem cells under appropriate conditions to obtain seed autologous adipose-derived stem cells, and freezing; finally, the amplified seed autologous adipose-derived stem cells are transported to a hospital through a cold chain, the autologous adipose-derived stem cells are infused back into the body of the liver disease patient in the hospital in an intravenous injection mode, and the average cell amount of the autologous adipose-derived stem cells injected into the liver disease patient every time is 7.1 multiplied by 10⁷Each is 9.2 multiplied by 10⁸The injection is injected once every 8-10 days, 5 times of injection is one treatment course, and 10-20 treatment courses are required according to the liver fibrosis degree of a liver disease patient.

Cells are the basic structural and functional units of an organism, the human body is an organism consisting of about 40 trillion cells of 220 different tissues, and all life activities are completed by the cells. Stem cells (stem cells) are a class of cells that are not fully differentiated and have the potential function of regenerating various tissues and organs, and have the functions of repairing tissues and organs, regulating immunity in vivo and the like. Cell therapy (cell therapy) refers to a treatment mode in which certain cells with specific functions are obtained by a bioengineering method or are treated by in vitro amplification, special culture and the like, and then are transfused into patients. The invention relates to a method for reversing hepatic fibrosis by applying stem cell therapy, belonging to cell therapy.

The invention has the beneficial effects that: the stem cell therapy of the present invention can bring new hopes for the treatment of patients with liver diseases, and the stem cell therapy of the present invention mainly has the following functions: the stem cell therapy of the invention can be safely used when applied to the treatment of liver diseases. The stem cell therapy of the invention can safely and effectively treat liver diseases and can restore the liver functions of patients with end-stage liver diseases. Numerous study results have shown that serum albumin levels in patients can be significantly elevated after 24 weeks of treatment by the stem cell therapy of the present invention. The stem cell therapy provided by the invention can obviously reverse liver fibrosis of a liver disease patient, and can relieve fatigue, pain and itch and improve the life quality of the liver disease patient.

Drawings

FIG. 1 serum albumin levels in a patient can be significantly elevated after 24 weeks of treatment by stem cell therapy;

FIG. 2 is a comparative liver plot showing that liver fibrosis can be significantly reversed in patients with liver disease by stem cell therapy; FIG. 3 is a graph comparing fibrosis index for significant reversal of liver fibrosis in liver disease patients by stem cell therapy;

FIG. 4 is a graph comparing the ability of the stem cell therapy of the present invention to significantly alleviate fatigue and pain and itch in patients.

Detailed Description

The present invention will be described in detail with reference to specific embodiments.

A method for reversing liver fibrosis by applying stem cell therapy specifically comprises the following steps: firstly, extracting autologous adipose-derived stem cells from a liver disease patient, then transporting the autologous adipose-derived stem cells to a GMP laboratory under the aseptic and cold chain conditions, wherein the GMP laboratory adopts a biological laboratory which meets the international cell preparation quality management system standard, and the starting autologous adipose-derived stem cells are obtained in a separation mode in the GMP laboratory; culturing, amplifying and purifying the initial autologous adipose-derived stem cells under appropriate conditions to obtain seed autologous adipose-derived stem cells, and freezing; finally, the amplified seed autologous adipose-derived stem cells are transported to a hospital through a cold chain, the autologous adipose-derived stem cells are infused back into the body of the liver disease patient in the hospital in an intravenous injection mode, and the average cell amount of the autologous adipose-derived stem cells injected into the liver disease patient every time is 7.1 multiplied by 10⁷Each is 9.2 multiplied by 10⁸The injection is injected once every 8-10 days, 5 times of injection is one treatment course, and 10-20 treatment courses are required according to the liver fibrosis degree of a liver disease patient. The stem cell therapy provided by the invention can obviously reverse liver fibrosis of a liver disease patient, and can also obviously improve fatigue, pain and itch symptoms of the liver disease patient, so that the life quality of the liver disease patient is improved.

Finally, it should be noted that the above-mentioned contents are only used for illustrating the technical solutions of the present invention, and not for limiting the protection scope of the present invention, and that the simple modifications or equivalent substitutions of the technical solutions of the present invention by those of ordinary skill in the art can be made without departing from the spirit and scope of the technical solutions of the present invention.

Claims

1. A method of reversing liver fibrosis using stem cell therapy, comprising: the method for reversing hepatic fibrosis by applying the stem cell therapy specifically comprises the following steps: firstly, extracting autologous adipose-derived stem cells from a liver disease patient, then transporting the autologous adipose-derived stem cells to a GMP laboratory under the aseptic and cold chain conditions, wherein the GMP laboratory adopts a biological laboratory which meets the international cell preparation quality management system standard, and the starting autologous adipose-derived stem cells are obtained in a separation mode in the GMP laboratory; culturing, amplifying and purifying the initial autologous adipose-derived stem cells under appropriate conditions to obtain seed autologous adipose-derived stem cells, and freezing; finally, the amplified seed autologous adipose-derived stem cells are transported to a hospital through a cold chain, the autologous adipose-derived stem cells are infused back into the body of the liver disease patient in the hospital in an intravenous injection mode, and the average cell amount of the autologous adipose-derived stem cells injected into the liver disease patient every time is 7.1 multiplied by 10⁷Each is 9.2 multiplied by 10⁸The injection is injected once every 8-10 days, 5 times of injection is one treatment course, and 10-20 treatment courses are required according to the liver fibrosis degree of a liver disease patient.