CN116919992A

CN116919992A - Application of stem cell exosome in preparation of medicines for treating cardiac hypertrophy

Info

Publication number: CN116919992A
Application number: CN202311098484.3A
Authority: CN
Inventors: 姬广聚; 杨智广; 毕友坤; 宋邵乐
Original assignee: Yuansheng Biotechnology Qingdao Co ltd
Current assignee: Yuansheng Biotechnology Qingdao Co ltd
Priority date: 2023-08-29
Filing date: 2023-08-29
Publication date: 2023-10-24

Abstract

The application provides an application of stem cell exosomes, in particular to an application of stem cell exosomes in preparing a medicament for preventing and/or treating myocardial injury, which is characterized in that the myocardial injury is caused by aortic arch constriction surgery. The stem cell exosome can reverse the reduction of the ejection fraction and the short axis shortening rate of the mice caused by the TAC operation, improve the expression level of SERCA2a mRNA and improve the heart function reduction caused by the TAC operation to a certain extent.

Description

Application of stem cell exosome in preparation of medicines for treating cardiac hypertrophy

Technical Field

The application relates to the technical field of biology, in particular to application of stem cell exosomes in preparation of medicines for treating myocardial hypertrophy.

Background

Cardiovascular disease is a group of diseases involving the heart or blood vessels, including coronary artery disease, stroke, heart failure, hypertensive heart disease, rheumatic heart disease, cardiomyopathy, abnormal heart rhythm, congenital heart disease, valvular heart disease, cardiac inflammation, aortic aneurysm, peripheral arterial disease, thromboembolic disease, venous thrombosis, and the like. Currently, cardiovascular disease is the leading cause of death in other parts of the world beyond continents. Cardiovascular disease is a major cause of human health and life loss, and is also the leading disease burden worldwide.

Any cardiovascular disease may lead to heart damage. Coronary artery disease, including hypertension, hypercholesterolemia, diabetes, obesity, history of familial heart failure, propensity for myocardial disease, and exposure to cardiotoxic drugs (e.g., alcohol, cancer treatment, and radiation), are all risk factors leading to myocardial injury.

The mouse aortic arch constriction (transverse aortic constriction, TAC) procedure achieves varying degrees of constriction of the aortic arch by binding needles of varying diameter sizes outside the aortic arch, resulting in higher aortic pressures and faster blood flow rates at the ligation. The increase in pressure stimulates the heart to increase the mass and volume of cardiomyocytes, increasing the thickness of the ventricular wall to maintain normal heart function; as pressure continues to stimulate, the heart fails to maintain its original heart function, and the heart may develop further toward heart failure. The heart has serious ventricular dilatation, myocardial apoptosis, myocardial fibrosis and other phenomena.

Currently, myocardial repair is not uniform, and is usually required to be administered according to different etiologies. Studies have shown that stem cell exosomes can be used to treat myocardial injury caused by Doxorubicin (Doxorubicin), but it is not known whether stem cell exosomes can improve TAC-induced myocardial hypertrophy and heart failure.

Disclosure of Invention

Based on the above, the application provides an application of stem cell exosomes in preparing medicines for treating cardiac hypertrophy.

According to one aspect of the present application, there is provided the use of a stem cell exosome for the manufacture of a medicament for the prevention and/or treatment of myocardial hypertrophy resulting from aortic arch constriction surgery.

In some embodiments, the stem cell exosome is a human embryonic stem cell exosome, a murine embryonic stem cell exosome, or an induced pluripotent stem cell exosome.

In some embodiments, the medicament comprises the stem cell exosomes and pharmaceutically acceptable excipients.

In some embodiments, the pharmaceutically acceptable adjuvant is selected from at least one of diluents, binders, wetting agents, disintegrants and lubricants.

In some embodiments, the diluent is selected from at least one of starch, dextrin, sucrose, glucose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, calcium sulfate, dibasic calcium phosphate, and calcium carbonate;

and/or the binder is at least one selected from starch slurry, dextrin, syrup, honey, glucose solution, microcrystalline cellulose, acacia slurry, gelatin slurry, sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, acrylic resin, carbomer, polyvinylpyrrolidone and polyethylene glycol;

and/or the disintegrating agent is at least one selected from starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, polyoxyethylene, sorbitol, fatty acid ester and sodium dodecyl sulfonate;

and/or the lubricant is at least one selected from talcum powder, silicon dioxide, stearate, tartaric acid, liquid paraffin and polyethylene glycol;

and/or the wetting agent is at least one selected from water, ethanol and isopropanol.

In some embodiments, the drug is administered by injection, orally or topically.

In some embodiments, the pharmaceutical dosage form is a capsule.

In some embodiments, the pharmaceutical dosage form is an oral liquid, an oral granule, or an oral powder.

In some embodiments, the pharmaceutical dosage form is a tablet.

In some embodiments, the pharmaceutical dosage form is an injection.

The application has the following beneficial effects:

according to the application, the stem cell exosome is used for preventing and/or treating myocardial hypertrophy caused by TAC operation for the first time through research, and the effect of the medicine is verified on a TAC mouse model, and the result shows that the stem cell exosome can improve the ejection fraction and short axis shortening rate of the mouse, improve the expression level of SERCA2a mRNA and improve the heart function reduction caused by TAC operation to a certain extent.

Drawings

In order to more clearly illustrate the technical solution in the embodiments of the present application and to more fully understand the present application and its advantageous effects, the following brief description will be given with reference to the accompanying drawings, which are required to be used in the description of the embodiments. It is evident that the figures in the following description are only some embodiments of the application, from which other figures can be obtained without inventive effort for a person skilled in the art.

FIG. 1 is a graph showing the results of identifying extracted embryonic stem cell exosomes in example 1; a is a transmission electron microscope image of a human embryonic stem cell exosome after negative staining, the scale is 100nm, B is a surface marker protein immunoblotting (WB) result of the embryonic stem cell exosome, and the loading amount is 5 mug;

FIG. 2 is a graph showing aortic arch blood flow analysis after TAC surgery in example 2; a is an aortic arch ultrasonic image of a mice in the sham operation group, B is an aortic arch ultrasonic image of a mice in the TAC group, C is an aortic arch blood flow velocity image of the mice in the sham operation group, and D is an aortic arch blood flow velocity image of the mice in the TAC group;

FIG. 3 is a statistical chart of cardiac ultrasound results of TAC mice in example 2; the method comprises the steps that A is a change curve of ejection fraction of a TAC mouse and a sham operation group mouse, B is a change curve of short-axis shortening rate of the TAC mouse and the sham operation group mouse, C is a change curve of room interval thickness of the TAC mouse and the sham operation group mouse, and D is a change curve of diastolic left ventricle inner diameter of the TAC mouse and the sham operation group mouse; n=3-5, data expressed as mean±sem, x represents p <0.05; * Represents p <0.01; * Represents p <0.001;

FIG. 4 shows the effect of TAC mice in example 3 using embryonic stem cell exosome intervention; a is a cardiac ultrasound image of a sham-operated group of mice, a TAC-operated group of mice and an embryonic stem cell exosome-operated group of mice, B is a change curve of ejection fraction (EF%) of the sham-operated group of mice, the TAC-operated group of mice and the embryonic stem cell exosome-operated group of mice, C is a change curve of short axis shortening rate (FS%) of the sham-operated group of mice, the TAC-operated group of mice and the embryonic stem cell exosome-operated group of mice, D is a result of SERCA2a mRNA level of the sham-operated group of mice, the TAC-operated group of mice and the embryonic stem cell exosome-operated group of mice, n=3-5, the data are expressed by mean+ -SEM.

Detailed Description

The detailed description of the present application will be provided to make the above objects, features and advantages of the present application more obvious and understandable. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present application. The present application may be embodied in many other forms than described herein and similarly modified by those skilled in the art without departing from the spirit of the application, whereby the application is not limited to the specific embodiments disclosed below.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein in the description of the application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. Unless otherwise specifically indicated, the various raw materials, reagents, instruments, equipment and the like used in the present application are commercially available or may be prepared by existing methods.

Some embodiments of the present application provide for the use of stem cell exosomes in the manufacture of a medicament for the prevention and/or treatment of myocardial hypertrophy caused by aortic arch constriction surgery.

Embryonic stem cells are primitive, highly undifferentiated cells that can differentiate into more than two hundred cell types under specific conditions. The exosomes are vesicles with diameters of 30-150 nm and phospholipid bilayer structures; can be involved in immunomodulation, migration, proliferation, apoptosis, autophagy, etc.

In some embodiments, the medicament comprises a stem cell exosome and a pharmaceutically acceptable adjuvant.

It is understood that "drug" in the present application includes any agent, compound, composition or mixture that provides a physiological and/or pharmacological effect in vivo or in vitro, and often provides a beneficial effect. The range of physiological and/or pharmacological actions of the "drug" in the body is not particularly limited, and may be systemic or may be local. The activity of the "drug" is not particularly limited, and may be an active substance capable of interacting with other substances or an inert substance which does not interact with other substances.

In one example, the drug may be a liquid formulation or a solid formulation. Liquid formulations refer to formulations containing a liquid phase, such as, without limitation, solutions, suspensions, emulsions, and the like. Non-limiting examples of solid formulations are tablets, capsules, granules, pills, and the like.

In one example, depending on the mode of administration, oral agents, injections, drops, patches, tube feeding formulations, and the like may be used.

In one example, the selected excipients may vary depending on the dosage form.

In the present application, "auxiliary materials" include, but are not limited to, mannitol, sorbitol, sodium metabisulfite, sodium bisulphite, sodium thiosulfate, cysteine hydrochloride, thioglycollic acid, methionine, disodium vitamin C, EDTA, calcium sodium EDTA, monovalent alkali metal carbonates, acetates, phosphates or aqueous solutions thereof, hydrochloric acid, acetic acid, sulfuric acid, phosphoric acid, amino acids, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivatives, cellulose and derivatives thereof, alginates, gelatin, polyvinylpyrrolidone, glycerol, tween 80, agar, calcium carbonate, calcium bicarbonate, surfactants, polyethylene glycol, cyclodextrin, phospholipids, kaolin, talc, calcium stearate, magnesium stearate.

In the present application, "pharmaceutically acceptable" refers to those ligands, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for administration to patients and commensurate with a reasonable benefit/risk ratio.

In the present application, "pharmaceutically acceptable excipients" refers to pharmaceutically acceptable materials, compositions or vehicles, such as liquid or solid fillers, diluents, excipients, solvents or encapsulating materials. As used herein, the language "pharmaceutically acceptable carrier" includes buffers compatible with pharmaceutical administration, sterile water for injection, solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like. Each body must be "pharmaceutically acceptable" in the sense of being compatible with the other ingredients of the formulation and not deleterious to the patient. Suitable examples include, but are not limited to: (1) sugars such as lactose, glucose and sucrose; (2) Starches, such as corn starch, potato starch, and substituted or unsubstituted beta-cyclodextrin; (3) Cellulose and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose, and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) Oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; (10) glycols, such as propylene glycol; (11) Polyols such as glycerol, sorbitol, mannitol and polyethylene glycol; (12) esters such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) ringer's solution; (19) ethanol; (20) phosphate buffer; and (21) other non-toxic compatible substances employed in pharmaceutical formulations.

In one example, the "acceptable excipients" are selected from at least one of diluents, binders, wetting agents, disintegrants and lubricants.

Specifically, the diluent is at least one selected from starch, dextrin, sucrose, glucose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, calcium sulfate, calcium hydrogen phosphate and calcium carbonate; the binder is at least one selected from starch slurry, dextrin, syrup, mel, glucose solution, microcrystalline cellulose, acacia slurry, gelatin slurry, sodium carboxymethylcellulose, methylcellulose, hydroxypropyl methylcellulose, ethylcellulose, acrylic resin, carbomer, polyvinylpyrrolidone and polyethylene glycol; the disintegrating agent is at least one selected from starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, crosslinked polyvinylpyrrolidone, crosslinked sodium carboxymethyl cellulose, sodium carboxymethyl starch, polyoxyethylene, sorbitol, fatty acid ester and sodium dodecyl sulfonate; the lubricant is at least one of talcum powder, silicon dioxide, stearate, tartaric acid, liquid paraffin and polyethylene glycol; the wetting agent is at least one selected from water, ethanol and isopropanol.

In one example, the medicament comprises an effective amount of stem cell exosomes.

In the present application, an "effective amount" refers to the amount of the component to which the term corresponds to effect treatment, prevention, alleviation and/or relief of a particular disease, disorder and/or condition in a subject, and in the present application, unless otherwise specified, refers to the amount to effect treatment, prevention, alleviation and/or relief of a liver disease, disorder and/or condition.

In the present application, a "subject" is an animal, preferably a mammal, more preferably a human, and includes, but is not limited to, a consumer of a nutraceutical and a patient having a disease, disorder, and/or symptom. The subject of the present application is preferably a mammal. The term "mammal" refers primarily to warm-blooded vertebrates, including but not limited to: such as cats, dogs, rabbits, bears, foxes, wolves, monkeys, deer, mice (e.g., rats, mice), pigs, cows, sheep, horses, humans, etc., preferably primates, more preferably humans.

In one example, the subject is a mammal.

In one example, the subject is a human or mouse.

In the present application, "patient" means an animal, preferably a mammal, more preferably a human. The term "mammal" refers primarily to warm-blooded vertebrates, including but not limited to: such as cats, dogs, rabbits, bears, foxes, wolves, monkeys, deer, mice, pigs, cattle, sheep, horses, humans, etc., preferably primates, more preferably humans.

The present application will be further described with reference to specific examples and comparative examples, which should not be construed as limiting the scope of the application.

Example 1: extraction and identification of exosomes of embryonic stem cells

Human embryonic stem cells h9 are spread in a culture dish coated by matrigel, and the culture medium is hESC-ncTarget. Changing liquid every day, when cells grow full, adding EDTA cell passage working liquid to digest cells according to the ratio of 1: and 8 passages.

Extracting the exosomes of the embryonic stem cells by adopting an ultracentrifugation method. The method comprises the steps of collecting cell supernatant of stem cells from human embryo sources, removing dead cells and cell fragments through gradient centrifugation, and finally obtaining semitransparent gelatinous precipitate through ultracentrifugation, namely the exosome of the stem cells of the embryo. The pellet was resuspended in PBS and the concentration of embryonic stem cell exosomes was determined by the brandford method (coomassie brilliant blue method). The obtained embryonic stem cell exosomes are subjected to negative staining by an osmium acid dye, and observed under a transmission electron microscope, the result is shown in fig. 1, and the embryonic stem cell exosomes can be clearly seen to have a typical cup-disc-shaped structure with a diameter of about 100nm (A in fig. 1). Dynamic light scattering can more accurately measure the size of the embryonic stem cell exosomes, and the average diameter of the embryonic stem cell exosomes is 89.99nm by calculation. In addition, markers on the exosome of embryonic stem cells were also detected by the Western Blotting (WB) method. CD63 and Tsg101 are enriched in embryonic stem cell exosomes (B in fig. 1), consistent with the protein sorting enrichment pathway of embryonic stem cell exosomes.

Example 2: construction of TAC mouse model

The method is a minimally invasive operation, and can effectively reduce the damage to the mice. The method comprises the following steps:

(1) Preoperative preparation: sterilizing all required surgical instruments one day before surgery

(2) A single intraperitoneal injection of ketamine (51.4 mg/kg) with a physiological saline (0.9% NaCl) solution of promethazine (3.3 mg/kg). After deep anesthesia, the neck and chest of the mice were dehaired with depilatory cream (purchased from dropsy), and the dehaired sites were sterilized with 75% alcohol. The mice were placed supine on a clean cork work pad and the paws were secured with tape. The whole operation process adopts aseptic operation technology.

(3) Skin was cut off from the centre of the chest, exposing the sternum. The thyroid gland was retracted using a 4/0 polypropylene suture and secured to the work pad with tape. The anterior tracheal muscles are separated, exposing the trachea. Gently slide the smoothly tipped curved microsurgical forceps, place the closed mandible behind the trachea and sternum, carefully open and close the microsurgical forceps to remove the pleura. The right collarbone upper muscle was grasped with a straight microsurgery forceps with a smooth tip, and the chest of the animal was gently pulled up. The upper sternum of 3-4 mm is cut using a bone forceps. The 7/0 polypropylene suture thread is used to pass through the second rib gaps on the two sides from inside to outside, and the suture thread is fixed on the working pad by the adhesive tape

(4) The tracheal anterior muscle, mediastinal fat and thymus were gently removed, the aortic arch was exposed, and the soft tissues surrounding the aortic arch were removed. A length of 6/0 ligature was passed under the aortic arch and removed between the right innominate artery and the left common carotid artery. The 27 gauge needle is placed over the aortic arch and needle are tied tightly together with a ligature, and then tied to two knots to prevent the previous knots from loosening. After which the needle is withdrawn quickly and gently.

(5) Sutures used to secure the sternum and thyroid were removed and the muscles and skin of the mice were sutured using 6-0 absorbable sutures. Mice were transferred to a separate cage and placed in the prone position. The mice were allowed to recover on the heating pad until fully awake. The analgesic is injected into the abdominal cavity after operation, and the subcutaneous injection is repeated to relieve pain. Cardiac ultrasound was performed for one week, two weeks, three weeks, and four weeks, respectively, after the operation. Echocardiography was recorded using a 30mHz probe and a Vevo 770 sonicator (VisualSonics, toronto, ON, canada). Vevo 770 is equipped with ECG-gated kilohertz visualization software. The hair on the chest of the mice is removed by the depilation cream, and the skin after depilation is wiped clean. After isoflurane anesthesia, the mice are fixed on a temperature control plate (37+/-1 ℃), couplant is coated on the chest, the instrument is adjusted to be B-mode, a probe is placed at the position of the sternum to the left, a long axis image of the left ventricle is obtained, the probe is rotated by 90 degrees to obtain a short axis image of the left ventricle, and an M mode is used for recording a cardiac ultrasonogram. The parameters of the heart were measured on the echocardiogram using the Vevo 770 software. The heart rate of the mice was controlled at 450.+ -.50 beats/min. The results of the ultrasound are shown in fig. 2, showing that in mice post TAC surgery, the aortic arch is ligated between the innominate artery and the left common carotid artery, and blood flow velocity at the ligation is much higher than in the non-ligated mice.

As shown in fig. 3, the ejection fraction (a) and short axis shortening rate (B) of the mice after TAC surgery increased in the first two weeks and significantly decreased in the third and fourth weeks; the thickness of the ventricular septum increases with time (C), the diastolic left ventricular inner diameter (D) becomes significantly greater around the fourth week; indicating successful TAC surgery, this model can be used for subsequent studies.

Example 3: improvement of cardiac function decline by TAC by embryonic stem cell exosomes

To investigate the repair effect of human embryonic stem cell-derived exosomes on TAC causing myocardial damage, a certain amount of embryonic stem cell exosomes was injected intravenously into the tail of mice twice a week, starting one week after TAC surgery. The heart function of the mice was examined ultrasonically at week five.

(1) Mouse cardiac ultrasound detection

Echocardiography was recorded using a 30mHz probe and a Vevo 770 sonicator (VisualSonics, toronto, ON, canada). Vevo 770 is equipped with ECG-gated kilohertz visualization software. The hair on the chest of the mice is removed by the depilation cream, and the skin after depilation is wiped clean. After isoflurane anesthesia, the mice are fixed on a temperature control plate (37+/-1 ℃), couplant is coated on the chest, the instrument is adjusted to be B-mode, a probe is placed at the position of the sternum to the left, a long axis image of the left ventricle is obtained, the probe is rotated by 90 degrees to obtain a short axis image of the left ventricle, and an M mode is used for recording a cardiac ultrasonogram. The parameters of the heart were measured on the echocardiogram using the Vevo 770 software. The heart rate of the mice was controlled at 450.+ -.50 beats/min.

The results of the ultrasound are shown in fig. 4 a, and five weeks after TAC surgery, both the ejection fraction and the short axis shortening rate of TAC group mice were significantly reduced. Mice injected with embryonic stem cell exosome intervention had significantly higher ejection fraction (B in fig. 4) and short axis shortening (C in fig. 4) than the TAC group. The exosomes of embryonic stem cells improve to some extent the heart function decline caused by TAC surgery.

(2) mRNA expression level detection of SERCA2a

SERCA2a is a critical protein in the calcium cycle of cardiomyocytes for uptake of calcium ions (Ca ²⁺ ) Entry into the sarcoplasmic reticulum causes diastole of the cardiomyocytes, thereby maintaining intracellular Ca ²⁺ And (3) steady state. It was studied that in TAC-induced heart failure, the expression level of SERCA2a was decreased, and that overexpression of this protein by the heart muscle improved heart failure. Thus, the amount of SERCA2a expression was detected by fluorescent quantitative PCR.

Preparation of RNA samples: taking 20mg of tissue, adding 1ml of TRIZOL, shearing, grinding into homogenate, and performing on ice in the whole process; placing on ice for 10min; 200 μl of chloroform is added, and the vortex is carried out for 15s to ensure uniform mixing of the liquid; standing at room temperature for 2-3 min, and centrifuging at 12000rpm for 15min at 4 ℃; carefully sucking the supernatant into a new centrifuge tube, adding 500 μl of isopropanol, and slowly mixing; standing at room temperature for 10min at 4deg.C, and centrifuging at 12000rpm for 10min; the supernatant was discarded, 1ml of 80% ethanol was added for washing, and the mixture was centrifuged at 7500rpm at 4℃for 5min; after discarding the supernatant and after no significant liquid residue in the centrifuge tube, 20. Mu.l of RNase-free DEPC H was used ₂ O is dissolved; detecting the integrity of the RNA sample by agarose gel electrophoresis; the concentration and purity of the RNA samples were measured using a NanoDrop 2000. Reverse transcription was performed using the PrimeScriptTM RT reagent Kit with gDNAEraser (TaKaRa) kit.

Primer sequences for fluorescent quantitative PCR are shown in Table 1; the reaction system is shown in Table 2. Fluorescent quantitative PCR was performed on RoTorr-Gene Q (QIAGEN). 4 duplicate wells were set for each sample to reduce random errors. Data processing and analysis were then performed with Excel and GraphPad Prism 7.

TABLE 1

Numbering device	Primer name	Sequence (5 '-3')
			SEQ ID NO 1	mSERCA2a(F)	ACCGGCACACATTTGAAGAAG
SEQ ID NO 2	mSERCA2a(R)	CTCGTTGAGGATCAGCAAGG
			SEQ ID NO 3	mβ-actin(F)	GGACTGTTACTGAGCTGCGTT
SEQ ID NO 4	mβ-actin(R)	CGCCTTCACCGTTCCAGTT

TABLE 2

Reagent(s)	Dosage of
		2×SYBR Green qPCR mix	10μl
Upstream primer (F) (10. Mu.M)	0.8μl
		Downstream primer (R) (10. Mu.M)	0.8μl
cDNA(50mM)	0.1μl
		ddH ₂ O	8.3μl

The statistical results of fluorescent quantitative PCR are shown in FIG. 4 (D), in which the expression level of SERCA2a mRNA is significantly reduced 5 weeks after TAC surgery, and the protein is increased after stem cell exosomes are predicted.

The results of the above examples show that five weeks after TAC surgery, the ejection fraction and short axis shortening rate of mice are reduced, cardiac function is impaired, and myocardial cells are damaged. After stem exsufflation with embryonic stem cells, the ejection fraction and short axis shortening rate of mice are all significantly higher than that of the operation group. Left ventricular tissue was taken for RNA extraction and mRNA content of SERCA2a was detected by quantitative fluorescent PCR. The results show that the SERCA2a content of the TAC operation group is obviously reduced, and the mRNA level of the SERCA2a is increased after the intervention of the exosomes of the embryonic stem cells. The result shows that the exosome of the embryonic stem cells has a certain protection effect on the heart pressure load model caused by the aortic arch constriction (TAC) operation.

The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.

The above examples illustrate only a few embodiments of the application, which are described in detail and are not to be construed as limiting the scope of the application. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the application, which are all within the scope of the application. Accordingly, the scope of protection of the present application is to be determined by the appended claims.

Claims

1. Use of stem cell exosomes for the preparation of a medicament for the prevention and/or treatment of cardiac hypertrophy, characterized in that said cardiac hypertrophy is caused by aortic arch constriction surgery.

2. The use according to claim 1, wherein the stem cell exosome is a human embryonic stem cell exosome, a murine embryonic stem cell exosome or an induced pluripotent stem cell exosome.

3. The use according to any one of claims 1 to 2, wherein the medicament comprises the stem cell exosomes and pharmaceutically acceptable excipients.

4. The use according to claim 3, wherein the pharmaceutically acceptable excipients are selected from at least one of diluents, binders, wetting agents, disintegrants and lubricants.

5. The use according to claim 4, wherein the diluent is at least one selected from the group consisting of starch, dextrin, sucrose, glucose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, calcium sulfate, dibasic calcium phosphate and calcium carbonate;

6. The use according to any one of claims 1 to 2, wherein the medicament is administered by injection, orally or topically.

7. The use according to any one of claims 1 to 2, wherein the medicament is in the form of a capsule.

8. The use according to any one of claims 1 to 2, wherein the medicament is in the form of an oral liquid, an oral granule or an oral powder.

9. The use according to any one of claims 1 to 2, wherein the pharmaceutical dosage form is a tablet.

10. The use according to any one of claims 1 to 2, wherein the medicament is in the form of an injection.