A stem cell exosome composition and its use in treating male sexual dysfunction

Abstract

The application discloses a kind of compositions based on engineering stem cell exosome and its application in treating male sexual dysfunction.The composition includes mesenchymal stem cell exosome modified by genetic engineering, which displays bifunctional fusion polypeptide targeting TβRⅡ and LOXL2 on the surface. The fusion polypeptide integrates TβR-PEP with LOXL2-PEP through flexible linker, and introduces HIV-TAT penetrating peptide and self-assembly motif, forms nanoparticles to extend half-life. In vitro experiments show that the inhibition efficiency of the fusion polypeptide on TβRⅡ and LOXL2 is significantly better than that of single polypeptide, and can synergistically reverse fibrosis and promote angiogenesis. Animal experiments confirm that exosome loaded with fusion polypeptide significantly improves the erectile function of diabetic ED rats. The application provides a radical treatment scheme for male sexual dysfunction through double-target synergistic, long-acting delivery and multi-effect repair mechanism.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biological medicine, in particular to an exosome composition for treating male sexual dysfunction (ED) and a treatment method thereof. BACKGROUND

[0002] Male sexual dysfunction, especially erectile dysfunction (ED), is a common disease among men worldwide, affecting a large number of middle-aged and elderly population. The occurrence of ED is usually related to factors such as vascular dysfunction, nerve damage, hormonal imbalance, etc. Traditional treatment methods include oral drugs (such as sildenafil), hormone replacement therapy, surgical implantation of prostheses, etc., but these methods have side effects or limited efficacy, and some treatment methods cannot effectively improve the root cause of ED.

[0003] In recent years, stem cell therapy as a new regenerative medicine has attracted widespread attention due to its potential in tissue repair, immune regulation, and angiogenesis. Stem cells secrete exosomes, carrying various active molecules (such as miRNA, protein, lipid, etc.), which can regulate the cell microenvironment and promote tissue regeneration. However, current researches are mostly focused on the application of stem cell exosomes in wound repair, immune regulation, etc., while the application in the field of ED is still in the preliminary exploration stage.

[0004] The potential of stem cell exosomes in ED treatment mainly comes from their effects on angiogenesis, nerve repair, and cell signal regulation. The molecules such as miRNA, protein, and lipid contained in exosomes can regulate the expression of target proteins, thereby promoting local blood flow, repairing damaged tissues, and restoring sexual function. The present application optimizes the loading of specific resistance polypeptides or antibodies in exosomes, and innovatively targets the regulation of TGF-β1 / Smad3 signaling axis, thereby improving the sexual function of ED patients. SUMMARY

[0005] The present application aims to provide a stem cell exosome composition and its application in treating male sexual dysfunction.

[0006] Therefore, the present application discloses a stem cell exosome composition, which comprises mesenchymal stem cell-derived exosomes and polypeptides loaded in the exosomes, wherein the polypeptides comprise any one of TβR-PEP, LOXL2-PEP, and a fusion polypeptide.

[0007] Preferably, the amino acid sequence of TβR-PEP in the present application is CGVSLSCHNSGFC.

[0008] Preferably, the amino acid sequence of LOXL2-PEP in the present application is CKGGGQYC.

[0009] Preferably, the amino acid sequence of the fusion polypeptide of the present application is shown as SEQ ID NO. 1.

[0010] In one aspect, the present application also discloses the use of TβR-PEP in the preparation of a drug for treating male sexual dysfunction.

[0011] In one aspect, the present application also discloses the use of LOXL2-PEP in the preparation of a drug for treating male sexual dysfunction.

[0012] In one aspect, the present application also discloses the use of the fusion polypeptide in the preparation of a drug for treating male sexual dysfunction.

[0013] The beneficial effects of the present application are as follows:

[0014] (1) Double-target fusion polypeptide design: The fusion polypeptide synchronously blocks the TGF-β1 / Smad3 fibrosis signaling pathway and the collagen cross-linking process by targeting TβR II and LOXL2. Experiments show that its inhibition efficiency on the two targets (IC50 is 3.5 nM and 6.8 nM, respectively) is 2-3 times higher than that of single polypeptide. The introduction of HIV-TAT penetrating peptide and self-assembly motif prolongs the half-life of the polypeptide to 24 hours (2-3 hours for single polypeptide), and the polypeptide is targeted and enriched in the corpus cavernosum tissue (enrichment rate > 70%).

[0015] (2) Optimization of exosome delivery system: The membrane surface display of the fusion polypeptide is realized through LAMP2 fusion protein, and the targeting efficiency is 4 times higher than that of ordinary exosomes; miR-29b (inhibiting collagen synthesis) and SDF-1α (promoting endothelial cell migration) are loaded to form a "signal blocking-matrix remodeling-vascular repair" synergistic mechanism.

[0016] (3) Synergistic treatment advantage: In a diabetic ED rat model, the fusion polypeptide-exosome group (1 mg / kg) makes the ICP / MAP ratio recover to 0.78±0.05 (close to the normal level 0.82±0.06), the fibrosis area reduces to 8.9±1.3% (36.7±4.2% for the control group), and the eNOS expression increases to 1380±110 IOD (480±60 for the control group), which is significantly better than the single-target exosome group (p<0.01).

[0017] (4) Long-acting and safety: The self-assembled nanostructure prolongs the half-life of the drug to 24 hours, and the therapeutic effect of a single injection lasts for ≥7 days; long-term toxicity experiments show that there is no difference in liver and kidney function indicators between the treatment group and the normal group (p>0.05).

[0018] (5) Clinical translation potential: Compared with traditional PDE5 inhibitors (such as sildenafil or peptides), the present invention can reverse the pathological basis of ED and radically improve sexual function; the low immunogenicity and targeting of exosomes reduce the risk of systemic side effects. At the same time, the present invention also compared the TβR-PEP, LOXL2-PEP, and fusion peptides of the present invention with PDE5 inhibitors (sildenafil and peptides) loaded with exosomes in animal experiments. The results showed that the three peptides of the present invention had better effects on PDE5 inhibitors (sildenafil and peptides), and the ICP / MAP ratio was higher than that of PDE5 inhibitors (sildenafil and peptides, both ICP / MAP ratios <0.6) with significant differences. Detailed Implementation

[0019] Unless otherwise defined, 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 invention pertains. The terminology used herein in the specification of this invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0020] Unless otherwise specified, the reagents, methods, and equipment used in this invention are conventional reagents, methods, and equipment in this technical field. Unless otherwise specified, the reagents and materials used in the following examples are all commercially available.

[0021] Example 1: Exosome source and preparation

[0022] 1. Cell Culture: In this embodiment, human umbilical cord mesenchymal stem cells (hUC-MSCs) were used as the source of exosomes. Umbilical cord MSCs are an ideal choice for exosome extraction due to the following advantages:

[0023] (1) Good secretion characteristics: hUC-MSCs have a high exosome secretion capacity and can release a large number of exosomes.

[0024] (2) Immunomodulatory capacity: Exosomes secreted by hUC-MSCs can regulate immune responses and have anti-inflammatory effects.

[0025] (3) Low immunogenicity: Compared with adult-derived stem cells, umbilical cord MSCs have a lower immune rejection response and are suitable for clinical treatment.

[0026] 2. Cell culture steps:

[0027] (1) Cell seeding: hUC-MSCs were isolated from umbilical cord tissue and cultured in DMEM medium containing 10% fetal bovine serum. Cells were seeded in pre-sterilized T75 culture flasks and cultured at 37°C in a 5% CO2 incubator.

[0028] (2) Cell passage: When the cells reach 80% confluence, they are digested with trypsin and passaged to maintain cell viability and proliferation capacity. At the 4th passage, cells with strong exosome secretion capacity are selected for the next experiment.

[0029] 3. Exosome extraction method: Exosomes secreted by hUC-MSCs were extracted using ultracentrifugation.

[0030] (1) Culture medium preparation: hUC-MSCs were cultured to the desired confluence (80%), and then replaced with serum-free culture medium (DMEM containing 0% FBS) and cultured for another 48 hours to promote exosome secretion.

[0031] (2) Collect the culture supernatant: Remove cells by centrifugation and collect the culture supernatant. First, centrifuge the culture supernatant at 3000×g for 10 minutes to remove cell debris and large particulate impurities.

[0032] (3) Preliminary separation of exosomes: The supernatant was centrifuged again at 10,000×g for 30 minutes to further remove larger cell debris and other impurities. At this point, most of the exosomes precipitated at the bottom of the centrifuge tube.

[0033] (4) Extraction of exosomes by ultracentrifugation: The final supernatant was transferred to a new centrifuge tube and ultracentrifuged at 100,000×g for 2 hours to concentrate and precipitate the exosomes.

[0034] (5) Resuspending exosomes: Resuspend the precipitated exosomes in PBS buffer and store at -80℃ for later use.

[0035] 4. Detection of exosomes

[0036] (1) The concentration of extracted exosomes was determined by protein quantification methods (such as the BCA method) or fluorescence detection methods (such as Nile Red staining). The results were all 1.2 × 10⁻⁶. 9 Particles / ml.

[0037] (2) The purity of exosomes was determined by nanoparticle tracking analysis (NTA). The results showed that the diameter of the exosomes was mainly concentrated between 50-150 nm and the particle size distribution was uniform, indicating that the extracted exosomes had high purity.

[0038] Example 2: Design and Synthesis of TβR-PEP

[0039] 1. Peptide Sequence Design: Based on the binding domain structure of TβRⅡ (Transforming Growth Factor β Receptor Type II), a resistance peptide targeting the TβRⅡ binding domain was designed. By analyzing the binding site of TβRⅡ, key amino acid residues were selected, and a resistance peptide with strong binding affinity was designed. The designed peptide sequence is as follows:

[0040] Peptide sequence: CGVSLSCHNSGFC; This peptide contains a disulfide bond to enhance its stability and spatial conformation stability, and is named TβR-PEP.

[0041] 2. Synthesis Method: Peptide synthesis was performed using solid-phase peptide synthesis (SPPS). The specific steps are as follows:

[0042] (1) Selection of resin and amino acid pretreatment: Rink Amide MH resin was selected as the carrier resin, which is suitable for the synthesis of peptides with C-terminal carboxyl groups of the amide type. The initial amino acid was Fmoc-L-Cys(Trt) (for C-terminal cysteine), and the synthesis was carried out stepwise using amino acids protected by Fmoc.

[0043] (2) Synthesis process: The synthesis was performed using the Fmoc (9-fluorenylmethoxycarbonyl) protection method. After each addition of an Fmoc-amino acid, the Fmoc protecting group was removed using 4M piperidine. Each amino acid was activated using DIC (N,N'-diisopropylcarbodiimide) and HOBt (1-Hydroxybenzotriazole) to react with the amino acid to form a peptide chain. The addition reaction of each amino acid was controlled within 1-2 hours to ensure complete synthesis.

[0044] (3) Formation of disulfide bonds: After the polypeptide synthesis is completed, the protecting groups are removed and the solid support is washed. The polypeptide is detached from the resin to obtain a crude peptide. In order to introduce disulfide bonds, the synthesized polypeptide is dissolved in a buffer solution containing an oxidant (hydrogen peroxide) to induce the formation of disulfide bonds between cysteine ​​residues.

[0045] (4) Deprotection and purification of peptides: The protecting groups were removed by urethane and fluoride to complete the deprotection of the peptide chain and obtain the full-length peptide chain. The synthesized peptides were purified by HPLC to obtain the target peptide with a purity greater than 95%.

[0046] 3. Experimental Summary: The resistant peptide TβR-PEP targeting the TβRII binding domain was successfully synthesized using a solid-phase peptide synthesis method, with a peptide purity exceeding 95%. Its structure and quality were verified using HPLC and other analytical techniques, ensuring the reliability and applicability of this peptide in subsequent experiments.

[0047] Example 3: Design and Synthesis of LOXL2-PEP

[0048] LOXL2 (Lysyl Oxidase-Like 2) is an oxidase belonging to the lysine oxidase family. It is primarily involved in the modification of the extracellular matrix (ECM), particularly in the cross-linking of collagen and elastin. LOXL2 plays a crucial role in multiple biological processes, including tissue structural stability, cell migration, inflammatory responses, and fibrosis.

[0049] A major cause of erectile dysfunction (ED) is vascular dysfunction, typically manifested as penile vasoconstriction and insufficient blood flow. LOXL2 plays a crucial role in the remodeling of vascular smooth muscle cells and endothelial cells. Excessive LOXL2 expression may lead to excessive cross-linking of the extracellular matrix, thereby exacerbating vascular wall rigidity, affecting vasodilation, and causing poor blood flow, thus inducing ED. Due to the key role of LOXL2 in fibrosis, studies have shown that high LOXL2 expression may be associated with fibrosis of the corpora cavernosa. Fibrosis leads to structural changes in the corpora cavernosa, reducing engorgement volume and thus affecting penile erectile function. By enhancing extracellular matrix cross-linking, LOXL2 may reduce the elasticity and extensibility of the corpora cavernosa, leading to erectile dysfunction. During erection, the relaxation and contraction of smooth muscle cells play a crucial role. LOXL2 may affect smooth muscle function by regulating extracellular matrix cross-linking of smooth muscle cells, further influencing the quality and duration of erection.

[0050] The above studies indicate that LOXL2 promotes fibrosis of the corpus cavernosum by catalyzing collagen fiber cross-linking, and its inhibitors can significantly reduce collagen deposition (experiments showed an inhibition rate >60%). Therefore, this study designed a resistant peptide LOXL2-PEP (amino acid sequence: CKGGGQYC, targeting the active site of LOXL2) to block its enzymatic activity. See Example 2 for the specific synthesis details.

[0051] Example 4: Design and synthesis of fusion peptides

[0052] Based on the designs in Examples 2 and 3, this study fuses two peptides into a single peptide, known as a fusion peptide. The specific design involves inserting a GGGGS flexible linker to separate the two functional domains and maintain their conformational independence; adding an HIV-TAT penetrating peptide (sequence: YGRKKRRQRRR) to the N-terminus to enhance transmembrane delivery efficiency; and introducing a VEWNEMTW hydrophobic sequence to the C-terminus to promote nanoparticle formation and prolong the in vivo half-life. The amino acid sequence of the fusion peptide after this design is shown in SEQ ID NO. 1. For specific synthesis details, please refer to Example 2.

[0053] Example 5: Applications of peptides and fusion peptides

[0054] I. Experiment 1: In vitro target binding and inhibition experiment

[0055] 1. Recombinant protein fixation: Recombinant human TβRII (100 ng / well) and LOXL2 (100 ng / well) were coated onto 96-well plates and incubated overnight at 4°C.

[0056] 2. Competitive ELISA: Biotin-labeled TGF-β1 (50 nM) or collagen IV (50 nM) were added as competitive ligands; gradient concentrations (0.1-1000 nM) of TβR-PEP, LOXL2-PEP, or fusion peptides were added respectively, and the mixture was incubated at 37°C for 1 hour; after washing, streptavidin-HRP was added, and OD450 was measured after color development.

[0057] 3. Data calculation: Calculate the half-maximal inhibitory concentration (IC50) and maximum inhibition rate (Imax) of each peptide.

[0058] 4. Experimental Results: The fusion peptide showed significantly better inhibitory efficiency against both targets than the single peptide (**p<0.01**), indicating a synergistic effect between the two targets. Details are shown in Table 1.

[0059] Table 1 Statistical analysis of test results

[0060]

[0061] II. Experiment 2: LOXL2 enzyme activity inhibition experiment

[0062] 1. Enzyme reaction system: LOXL2 (10 nM) and collagen IV (1 mg / mL) were incubated in a reaction buffer at 37°C for 24 hours; different treatments (single peptides or fusion peptides, final concentration 10 μM) were added.

[0063] 2. Detection of cross-linking products: The collagen cross-linking density (μg / mg) was determined by the hydroxyproline colorimetric method, and the LOXL2 activity (Ex / Em = 530 / 590nm) was detected by fluorescence method.

[0064] 3. Experimental Results: The fusion peptide exhibited 1.6 times the inhibitory effect on LOXL2 compared to the single peptide, and significantly reduced collagen cross-linking. Details are shown in Table 2.

[0065] Table 2 Results of LOXL2 enzyme activity inhibition assay

[0066]

[0067]

[0068] (*p<0.01 vs control group; **p<0.01 vs LOXL2-PEP group)

[0069] III. Experiment 3: Anti-fibrotic cell experiment (HCSMC model)

[0070] 1. Cell treatment: Human corpus cavernosum smooth muscle cells (HCSMCs) were divided into 5 groups: control group (no treatment), TGF-β1 group (10 ng / mL TGF-β1, 48 hours), TGF-β1+TβR-PEP group (10 μM), TGF-β1+LOXL2-PEP group (10 μM), and TGF-β1+fusion peptide group (10 μM).

[0071] 2. Detection indicators: Western blot was used to detect the expression of α-SMA, Collagen I, and p-Smad3 proteins; immunofluorescence was used to observe the cytoskeleton (F-actin staining).

[0072] 3. Experimental Results: The fusion peptide almost completely reversed the fibrosis indicators, significantly outperforming the single peptide (α-SMA inhibition rate: fusion peptide 65% vs TβR-PEP 44% vs LOXL2-PEP 34%). The results are shown in Table 3.

[0073] Table 3 Results of anti-fibrotic cell experiments

[0074]

[0075] (*p<0.05, **p<0.01 vs TGF-β1 group)

[0076] IV. Experiment 4: Angiogenesis Promoting Experiment (HUVEC Migration Model)

[0077] 1. Transwell migration assay: HUVEC cells were seeded in the upper chamber of a Transwell (serum-free medium); medium containing SDF-1α (50 ng / mL) was added to the lower chamber, and single peptides or fusion peptides (10 μM) were added respectively; after 24 hours, the cells were fixed, stained with crystal violet, and the number of migrating cells was counted.

[0078] 2. Angiogenesis experiment: HUVECs were seeded in Matrigel matrix, and lumen formation (length and number of branches) was observed.

[0079] 3. Experimental Results: The angiogenesis-promoting effect of the fusion peptide was 1.5-2 times that of the single peptide, suggesting that the dual targets synergistically activate endothelial function. Details are shown in Table 4.

[0080] Table 4 Results of the angiogenesis-promoting experiment

[0081]

[0082] (*p<0.05 vs. control group; **p<0.01 vs. single peptide group)

[0083] V. Summary:

[0084] 1. Dual-target synergy: The fusion peptide increased the inhibition efficiency of TβRII and LOXL2 by 2.3 times and 1.8 times, respectively;

[0085] 2. Complementary functions: TβR-PEP blocks fibrosis signals, LOXL2-PEP inhibits collagen cross-linking, and their combined effect reverses the pathological process;

[0086] 3. Long-lasting effect: The self-assembled nanostructure extends the half-life to 24 hours (compared to only 2-3 hours for a single peptide), and the efficacy of a single injection lasts for ≥7 days.

[0087] Example 6: Exosome-loaded peptides and their applications

[0088] The exosomes prepared in Example 1 were loaded with the three peptides from Examples 2-4 using an ultrasonic method. The loading efficiency was detected by fluorescence labeling and protein quantification analysis. The concentration of the peptides loaded onto the exosomes was adjusted to 1 mg / mL, and the loading efficiency was 82% ± 3.5%. This resulted in the formation of TβR-exo, OXL2-exo, and the fusion peptide-exo.

[0089] 1. Laboratory animals and grouping

[0090] (1) Animal selection: Male SD rats (weighing 250-300g) were purchased from the experimental animal center.

[0091] (2) Grouping: A total of 60 rats were randomly divided into 6 groups of 10 rats each:

[0092] ① Normal control group: Healthy rats that did not receive any intervention.

[0093] ②ED model group: diabetic ED rats were induced by STZ and treated with saline.

[0094] ③exo group: diabetic ED rats were injected with 1 mg / kg exosomes (exosomes prepared in Example 1) into the corpus cavernosum.

[0095] ④TβR-exo group: diabetic ED rats were injected with 1 mg / kg TβR-exo into the corpus cavernosum.

[0096] ⑤OXL2-exo group: diabetic ED rats were injected with 1 mg / kg OXL2-exo into the corpus cavernosum.

[0097] ⑥ Fusion peptide-exo group: diabetic ED rats were injected with 1 mg / kg fusion peptide-exo into the corpus cavernosum.

[0098] 2. Model Building

[0099] (1) STZ-induced diabetes:

[0100] ① Diabetes induction: A diabetic ED rat model was established by intraperitoneal injection of STZ (60 mg / kg).

[0101] ② Blood glucose detection: 48 hours after injection, the blood glucose level of rats was measured using a tail tip blood glucose meter. Rats with a blood glucose level ≥16.7 mmol / L were classified as diabetic rats.

[0102] ③ED diagnosis: The diagnostic criterion for ED is to measure the erectile function of rats (ICP / MAP ratio). ICP / MAP < 0.5.

[0103] 3. Experimental detection indicators

[0104] ①ICP / MAP ratio: Used to assess erectile function in rats. An ICP / MAP ratio > 0.5 indicates normal erectile function, while a ratio < 0.5 indicates erectile dysfunction.

[0105] ②Masson staining to quantify the fibrosis area of ​​the corpus cavernosum: The degree of fibrosis of the corpus cavernosum is detected by Masson's trichrome staining method, and the fibrosis area is quantified.

[0106] ③ Immunohistochemical detection of eNOS: used to assess the level of NO synthesized by vascular endothelium in rat corpora cavernosa, NO being a key regulator of erectile function.

[0107] 4. Experimental Procedure

[0108] (1) Diabetes model construction and evaluation: STZ-induced diabetes model, confirming that the blood glucose level of rats is ≥16.7mmol / L and the ICP / MAP ratio is <0.5, is used to establish the ED model.

[0109] (2) Drug treatment: The rats were then randomly grouped and treated with saline or different drug combinations.

[0110] (3) Treatment cycle: The treatment lasts for 4 weeks, with one injection per week.

[0111] (4) Detection

[0112] ① ICP / MAP ratio determination: The ratio between intracavernosal pressure (ICP) and mean arterial pressure (MAP) is measured using a rectal temperature probe connected to a pressure sensor.

[0113] ②Masson staining: After the rats were sacrificed, the corpora cavernosa of the penis were removed, fixed and sectioned. Masson's trichrome staining method was used to observe the fibrosis in the corpora cavernosa, and the fibrosis area was calculated using image analysis software.

[0114] ③ Immunohistochemistry: Immunohistochemistry was used to detect eNOS expression in the corpus cavernosum tissue and to observe angiogenesis and vascular function.

[0115] 5. Experimental results and data analysis are shown in Table 5.

[0116] (1) ICP / MAP ratio: The ICP / MAP ratio of the normal control group rats was 0.82±0.06, indicating normal erectile function. The ICP / MAP ratio of the ED model group rats was significantly reduced to 0.38±0.04, indicating erectile dysfunction in the diabetic ED model rats. Compared with the ED model group, the other four treatment groups all showed relatively good effects, with significant differences; and the fusion peptide-exo group had the best effect, close to the normal control group (p<0.01), showing the best efficacy.

[0117] (2) Fibrosis area: The ED model group showed significant fibrosis of the corpus cavernosum (36.7±4.2%), reflecting severe fibrosis and vascular dysfunction. Compared with the ED model group, the other four treatment groups all showed relatively good effects with significant differences; and the fusion peptide-exo group had the best effect, close to the normal control group (p<0.01), showing the strongest reversal effect.

[0118] (3) eNOS expression: eNOS expression was significantly decreased in the ED model group (480±60), indicating reduced NO synthesis and resulting in erectile dysfunction. Compared with the ED model group, the other four treatment groups all showed relatively good effects with significant differences; and the fusion peptide-exo group had the best effect, close to the normal control group (p<0.01), showing the best efficacy.

[0119] Table 5 Summary of Test Results

[0120]

[0121] 6. Conclusion and Discussion

[0122] The fusion peptide-exo group showed significant advantages in improving erectile function, reversing fibrosis, and promoting angiogenesis, with efficacy approaching that of the normal control group and significantly superior to the TβR-exo and LOXL2-exo groups. Furthermore, the combined treatment groups of the three peptides and exo were all better than the exo group. The therapeutic effect of the fusion peptide-exo group may be due to its simultaneous targeting of TβRⅡ and LOXL2, which can more effectively improve fibrosis and angiogenesis defects in diabetic erectile dysfunction.

[0123] Although the TβR-exo group and LOXL2-exo group improved erectile function and angiogenesis to some extent, their efficacy was more limited compared to the fusion peptide-exo group, but both were better than the exo group alone, indicating that the targeted peptide has a relatively significant effect.

[0124] Therefore, the treatment strategy of fusion peptide-exo groups provides a new and effective means for the treatment of diabetic erectile dysfunction, and its clinical translation potential is worth further investigation.

[0125] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A composition of stem cell exosomes, characterized in that, The composition comprises exosomes derived from mesenchymal stem cells and peptides loaded on the exosomes, wherein the peptides are fusion peptides of TβRⅡ-PEP and LOXL2-PEP; the amino acid sequence of TβRⅡ-PEP is CGVSLSCHNSGFC; the amino acid sequence of LOXL2-PEP is CKGGGQYC; and the amino acid sequence of the fusion peptide is shown in SEQ ID NO.

1.

2. The use of a fusion polypeptide in the composition of claim 1 in the preparation of a medicament for treating erectile dysfunction in men.

Images