Application of tryptophan metabolite in preparation of medicine for promoting stem cell repair

Abstract

The invention discloses an application of tryptophan metabolite in preparation of a medicine for promoting stem cell repair. The tryptophan metabolite disclosed by the invention is 5-hydroxy-3-indoleacetic acid. Related researches prove that the 5-hydroxy-3-indoleacetic acid not only can well promote proliferation and differentiation of stem cells in a normal physiological state, but also can promote repair of stem cells with damaged functions. Therefore, the 5-hydroxy-3-indoleacetic acid can be applied to preparation of a medicine for promoting stem cell repair and a stem cell culture medium additive.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and specifically relates to the application of a tryptophan metabolite in the preparation of a drug for promoting stem cell repair. Background Art

[0002] Stem cells (SC) are cells with self-replication and multidirectional differentiation potential. Under certain conditions, they can differentiate into multiple functional cells. On the one hand, stem cells have the ability of self-renewal and multidirectional differentiation. Under appropriate microenvironment and signal stimulation, they can differentiate into target cell types, such as cardiomyocytes, neurons, bone cells, etc., which can replace damaged or dead cells and promote tissue repair and regeneration. At present, with the aggravation of population aging and changes in lifestyle, the incidence of various chronic diseases such as cardiovascular and cerebrovascular diseases and neurodegenerative diseases is increasing. Stem cells, as cells with self-replication and multidirectional differentiation potential, have brought new hope for the treatment of these diseases. On the other hand, the organoids gradually formed by stem cells through self-renewal and directional differentiation under specific culture conditions provide important experimental models for studying organ development, disease mechanism, drug screening and personalized medicine. Therefore, discovering active factors that promote stem cell proliferation and developing efficient stem cell culture systems are of great value in many research fields such as regenerative medicine and disease treatment.

[0003] 5-Hydroxy-3-indoleacetic acid (5-HIAA) is an important metabolite downstream of tryptophan, which is mainly produced by the metabolism of the neurotransmitter serotonin (5-HT) under the action of monoamine oxidase. At present, studies have shown that the content of 5-HIAA in urine can reflect the metabolism of serotonin in the body. In clinical practice, by detecting the level of 5-HIAA in urine, it can assist in the diagnosis of some diseases related to abnormal serotonin metabolism, such as carcinoid syndrome.

[0004] The high incidence of diseases related to stem cell dysfunction has brought a heavy burden to patients and society. At present, there are many defects in the existing technologies in the field of stem cell repair. On the one hand, the methods for promoting stem cell repair are relatively limited, and the results are often unsatisfactory. Many existing technologies are not effective in promoting stem cell proliferation and differentiation, resulting in slow stem cell repair and difficulty in meeting clinical needs for rapid and efficient repair of damaged tissues. On the other hand, existing products for stem cell repair have deficiencies in process and performance. Some products may have large side effects, bringing additional health risks to patients. At the same time, the preparation process of existing products is complicated and the cost is high, which is not conducive to widespread application. Therefore, in-depth exploration of substances that can promote stem cell repair is of great research significance.

[0005] At present, the understanding of substances that play a key role in promoting the process of stem cell repair is still relatively limited, and there are few studies on stem cell repair using amino acid metabolites. Tryptophan can be decomposed into a series of indole homologues such as 5-hydroxy-3-indoleacetic acid, but the metabolites involved in the regulation of stem cell repair have not been reported. Summary of the invention

[0006] Purpose of the invention: The purpose of the present invention is to provide an application of a tryptophan metabolite in the preparation of a drug for promoting stem cell repair. The present invention has confirmed through relevant studies that 5-hydroxy-3-indoleacetic acid can promote the growth and differentiation of colon organoids after being administered to organoids, thereby improving the proliferation and differentiation function of stem cells, and can be used to promote stem cell repair. Therefore, the tryptophan metabolite 5-hydroxy-3-indoleacetic acid of the present invention can be used to prepare a drug for promoting stem cell repair and to prepare a stem cell culture medium additive.

[0007] Technical solution: The purpose of the present invention is achieved through the following technical solution:

[0008] The present invention provides an application of a tryptophan metabolite in the preparation of a drug for promoting stem cell repair. The tryptophan metabolite is 5-hydroxy-3-indoleacetic acid.

[0009] The present invention also provides an application of a tryptophan metabolite in the preparation of a stem cell culture medium additive, wherein the tryptophan metabolite is 5-hydroxy-3-indoleacetic acid.

[0010] Preferably, the drug comprises 5-hydroxy-3-indoleacetic acid or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.

[0011] Furthermore, the auxiliary material comprises one or more of an emulsifier, a binder, a diluent, a wetting agent, an antioxidant, a lubricant, a solubilizer, a preservative or a disintegrant.

[0012] The emulsifier is selected from at least one of Tweens, Spans, glycerol fatty acid esters, gelatin water, pectin, agar, sulfates, sodium alginate and silicon dioxide. The adhesive is selected from at least one of starch slurry, sodium carboxymethyl cellulose, povidone, hydroxypropyl cellulose, methyl cellulose and ethyl cellulose. The diluent is selected from at least one of starch, sugar, cellulose and inorganic salts. The wetting agent is selected from at least one of water and ethanol. The antioxidant is selected from at least one of ascorbic acid, sulfites, bisulfites, gallic acid and lipids. The lubricant is selected from at least one of magnesium stearate, talc, hydrogenated vegetable oil, polyethylene glycols and micro-powder silica gel. The solubilizer is selected from one of Tweens, polyoxyethylene fatty alcohol ethers, sulfates and sulfonates. The preservative is selected from at least one of benzoic acid and its salts, sorbic acid and its salts and parabens. The disintegrant is selected from at least one of starch, sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, low-substituted hydroxypropyl cellulose and cross-linked polyvinyl pyrrolidone.

[0013] Preferably, the effective dose of 5-hydroxy-3-indoleacetic acid in the drug is 50 μM.

[0014] Preferably, the dosage form of the drug is tablets, granules, oral liquid, capsules, pills, emulsions, suspensions, injections, ointments, sprays or patches.

[0015] Preferably, the drug is administered orally, by enema or by injection.

[0016] The experimental study of the present invention found that 5-hydroxy-3-indoleacetic acid has a significant promoting effect on the proliferation and differentiation of stem cells. The present invention established a mouse colon organoid model simulating a normal physiological state, and administered 5-hydroxy-3-indoleacetic acid after primary cell passage. On the fifth day after administration, bright field photography was performed to statistically analyze the budding rate and crypt domain indicators of the organoids. Compared with the control group, the colon organoids in the 50μM 5-hydroxy-3-indoleacetic acid administration group showed a significant improvement in the organoid budding rate and organoid crypt domain, indicating that 5-hydroxy-3-indoleacetic acid can enhance the proliferation and differentiation ability of stem cells under normal physiological conditions.

[0017] In order to verify the repairing effect of 5-hydroxy-3-indoleacetic acid on damaged stem cell proliferation and differentiation, the present invention uses a mouse with impaired proliferation and differentiation of intestinal stem cells induced by gene defects to simulate the pathological state of stem cells, establishes a colon organoid model simulating the pathological state of damaged stem cells, and administers 5-hydroxy-3-indoleacetic acid after primary cell passage. On the fifth day after administration, bright field photography is performed to count the budding rate and crypt domain indicators of the organoid. Compared with the control group, the budding rate and crypt domain of the colon organoid in the 50μM 5-hydroxy-3-indoleacetic acid administration group showed a significant increase, indicating that 5-hydroxy-3-indoleacetic acid can improve the ability of functionally impaired stem cells to proliferate and differentiate.

[0018] Therefore, 5-hydroxy-3-indoleacetic acid has a certain effect in promoting stem cell repair.

[0019] Beneficial effects:

[0020] The present invention confirms through relevant research that 5-hydroxy-3-indoleacetic acid can not only effectively promote the proliferation and differentiation of stem cells under normal physiological conditions, but also promote the repair of functionally impaired stem cells. The application of 5-hydroxy-3-indoleacetic acid in the preparation of drugs and stem cell culture medium additives for promoting stem cell repair not only explores the new medicinal value of 5-hydroxy-3-indoleacetic acid, but also has certain medical prospects and economic value. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 This is the design diagram of the 5-hydroxy-3-indoleacetic acid organoid drug administration experiment. Figure 1 A is a schematic diagram of extracting intestinal stem cells and culturing them to form organoids; Figure 1 B is the timeline of 5-hydroxy-3-indoleacetic acid organoid administration.

[0022] Figure 2 The effect of 5-hydroxy-3-indoleacetic acid on intestinal organoids under normal physiological conditions. Figure 2 A is a bright field photograph of intestinal organoids in each group on the fifth day of 5-hydroxy-3-indoleacetic acid administration; Figure 2 B is the statistical graph of the germination rate of intestinal organoids in each group on the fifth day of 5-hydroxy-3-indoleacetic acid administration; Figure 2 C is the statistical graph of the crypt areas of intestinal organoids in each group on the fifth day of 5-hydroxy-3-indoleacetic acid administration (**p<0.01, *p<0.05).

[0023] Figure 3 The effect of 5-hydroxy-3-indoleacetic acid on intestinal organoids under pathological conditions. Figure 3 A is a bright field photograph of intestinal organoids in each group on the fifth day of 5-hydroxy-3-indoleacetic acid administration; Figure 3B is the statistical graph of the germination rate of intestinal organoids in each group on the fifth day of 5-hydroxy-3-indoleacetic acid administration; Figure 3 C is the statistical graph of the crypt areas of intestinal organoids in each group on the fifth day of 5-hydroxy-3-indoleacetic acid administration (**p<0.01, *p<0.05). DETAILED DESCRIPTION

[0024] The technical solution of the present invention is described in detail below through specific embodiments, but the protection scope of the present invention is not limited to the embodiments.

[0025] If no specific techniques or conditions are specified in the examples, the techniques or conditions described in the literature in the field or the product instructions are used. If no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be purchased through regular channels.

[0026] The experimental methods in the following examples are conventional methods unless otherwise specified. The experimental materials used in the following examples are commercially available products unless otherwise specified.

[0027] Example 1 Effects of 5-hydroxy-3-indoleacetic acid on intestinal organoids under normal physiological conditions

[0028] In order to verify the promoting effect of 5-hydroxy-3-indoleacetic acid on the proliferation and differentiation of stem cells, the present embodiment established a mouse colon organoid model simulating a normal physiological state, and 5-hydroxy-3-indoleacetic acid was administered after primary cell passaging. Bright field photography was performed on the fifth day after administration, and the budding rate and crypt domain indicators of the organoids were counted to detect the improving effect of 5-hydroxy-3-indoleacetic acid on the growth and differentiation of stem cells.

[0029] Figure 1 A is a schematic diagram of the entire experimental design, including the extraction of intestinal stem cells, the culture of colon organoids, and the administration of organoids after passage; Figure 1 B is the timeline of 5-hydroxy-3-indoleacetic acid organoid administration for the specific implementation of the experiment.

[0030] (1) Experimental Materials

[0031] Mice: C57BL / 6J mice (female, 8 weeks old), 18-22 g, were purchased from Nanjing Jicui Yaokang Experimental Animal Co., Ltd.

[0032] 5-Hydroxyindole-3-acetic Acid (5-HIAA) (CAS No. 54-16-0) was purchased from Sigma-Aldrich;

[0033] Mouse IntestiCult TMComplete organoid growth medium, purchased from Stem Cell;

[0034] DMEM / F-12 (containing 15 mM HEPES) was purchased from Pronocell Biotechnology Co., Ltd.;

[0035] Basic Matrigel was purchased from Corning;

[0036] Other reagents were of the best quality available on the market.

[0037] (2) Solution preparation

[0038] Mouse intestinal organoid complete growth medium: add 1 mL of Supplement 1 and 1 mL of Supplement 2 (Stem Cell, 06002, 06003) to 18 mL of basal medium (Stem Cell, 06001), add 200 μL of 100× Penicillin / Streptomycin (MCE), and store at 4°C;

[0039] Washing solution: DMEM / F12 solution containing HEPES containing 1% 100× Penicillin / Streptomycin double antibody and 10% fetal bovine serum (FBS), stored at 4°C;

[0040] Collagenase solution: a wash solution containing 2 mg / mL collagenase I powder (Sigma-Aldrich) and 50 μg / mL gentamicin (stock solution is 50 mg / mL), stored at -20°C;

[0041] PBS-EDTA solution: 0.5 mM EDTA solution, dissolved in PBS solution, and sterilized by filtration through a 0.22 μm filter membrane;

[0042] Pancreatin: Accurately weigh 0.25 g pancreatin (Gibco) powder and 0.02 g EDTA powder and dissolve them in 100 mL PBS solution. Stir at low speed for 1 h, filter with a 0.22 μm filter membrane to sterilize, and store at 4°C.

[0043] 5-Hydroxy-3-indoleacetic acid solution: Accurately weigh 10 mg of 5-hydroxy-3-indoleacetic acid powder and dissolve it in 1.05 mL of ultrapure water. After complete dissolution, filter it with a 0.22 μm filter membrane for sterilization and store it at -20°C. When using, take 1 μL of it after thawing and add 1 mL of mouse intestinal organoid complete growth medium to prepare a culture medium containing 50 μM 5-hydroxy-3-indoleacetic acid.

[0044] (3) Extraction of colonic crypt stem cells under normal physiological conditions

[0045] After the mice were killed by cervical dislocation, the abdominal cavity was opened, the colon was removed and placed in a 90 mm culture dish, the colon was washed with ice HBSS buffer (Thermo Fisher), and the fat, mucosa and connective tissue on the intestine were scraped off with a sterilized slide. After washing, the intestinal segment was cut longitudinally, and after further washing, the intestinal segment was transferred to a 50 mL centrifuge tube containing ice HBSS buffer. After vigorous vortexing for 5 minutes, the intestinal segment was transferred to a 90 mm culture dish containing ice HBSS buffer and washed again twice. The intestinal segment was transferred to a 35 mm culture dish, and the colon was cut into small segments (<1 mm) with scissors. 2 ), add 3mL collagenase solution, and suspend the colon tissue fragments in the solution. Place the culture dish in a 37℃ cell culture incubator and incubate it. Use a 1mL pipette to blow several times every 10min, and then check under a microscope whether the single epithelial unit (crypt) is separated and detached from the tissue (this step takes about 40-60min, until most of the crypts are separated). Pass the collagenase solution containing tissue fragments through a 70μm cell filter and wash the filter with 9mL washing solution. Collect the filtrate and transfer it to a 15mL centrifuge tube. Centrifuge it at 80g at room temperature for 5min with a low-temperature high-speed centrifuge, then discard the supernatant with a pipette, and resuspend the precipitate with 1mL washing solution to obtain the extracted crypt stem cell suspension.

[0046] (4) Culture of colon organoids

[0047] The extracted intestinal crypt stem cells were counted: the crypt stem cells were resuspended in 1 mL of washing solution, mixed evenly by inversion, and 10 μL of the cell suspension was dropped into a 96-well cell culture plate containing 90 μL of washing solution. This was repeated 3 times and then counted under an optical microscope. The average of the 3 counts in each well was taken. After the average of the 3 wells was taken, the number of extracted crypt stem cells was obtained by multiplying the number of wash solutions added for resuspension by the corresponding multiple.

[0048] Preheat the 24-well cell culture plate in a cell culture incubator at 37°C for half an hour. TM The culture medium was placed at room temperature. The mouse crypt stem cells resuspended in the wash solution were counted and transferred to a 1.5 mL centrifuge tube. Centrifuge at 200 g for 5 min at room temperature, and the wash solution was carefully discarded as much as possible. The test tube was placed on ice, and the cell clumps in the centrifuge tube were resuspended with Matrigel matrix gel. 200 organoids / 15 μL / well were dropped into the preheated 24-well plate, and the cell culture plate was inverted in a 37°C cell culture incubator for 15 min. After the matrix gel solidified, 500 μL IntestiCult was carefully added to each well. TM Culture medium was used to culture the cells and observe the growth of organoids in real time. The culture medium was replaced at least every 2 days.

[0049] (5) Subculture of colon organoids

[0050] Prepare 24-well cell culture plates preheated to 37°C. TM The culture medium was placed at room temperature. After 6 days of culturing the crypts, the liquid culture medium was removed from each well. 500 μL PBS-EDTA was added for washing, and then discarded. 200 μL of trypsin was added to each well, and the spherical matrix containing the organoids was broken by blowing and aspirating with a 1 mL pipette moistened with trypsin, and the cell plate was cultured in a cell culture incubator at 37°C for 5 minutes. The cell plate was removed, 800 μL of wash solution was added to each well, and after blowing and beating, the suspension was transferred to a 15 mL centrifuge tube and 5 mL of wash solution was added. The suspension was centrifuged at 200 g for 5 minutes at room temperature, and the supernatant was carefully poured off. 1000 μL of wash solution was added to resuspend the cell clumps, and the cell clumps were centrifuged at 200 g for 5 minutes at room temperature, and the wash solution was discarded. Resuspend the cell aggregates with an appropriate volume of Matrigel (200 organoids / 15 μL / well drop according to the count under the microscope), drop 15 μL / well into a preheated 24-well plate, and incubate the cell culture plate upside down in a 37°C cell culture incubator for 15 min to allow the matrix gel to solidify.

[0051] (6) 5-Hydroxy-3-indoleacetic acid administration experiment in colon organoids

[0052] The organoids were divided into a normal control group (CON, no drug group) and a 50μM 5-hydroxy-3-indoleacetic acid (5-HIAA) drug group. The same number of intestinal crypt stem cells were seeded in a 24-well cell culture plate with a seeding density of 200 organoids / 15μL / well. After culturing in a cell culture incubator for 5 days, the cell growth state was observed and photographed under a Leica DMI 3000B fluorescence inverted microscope.

[0053] The definition is based on the spherical structure of intestinal organoids and the typical intestinal organoid structure defined by the Intestinal Stem Cell Association (NIH). The morphology and structure during growth are photographed under a microscope. Without overlapping the field of view, one photo is regarded as a point, and the number of budding organoids and the total number of organoids (including those that have sprouted and those that have not sprouted) are counted. The organoid sprouting rate = the number of budding organoids / the total number of organoids.

[0054] Crypt domain refers to the number of small spherical organoids generated at the tip of the intestinal organoid. Organoid crypt domain = total crypt domain / number of budding organoids.

[0055] The experimental data are expressed as Mean ± SEM, and the results were analyzed and processed using GraphPad Prism 8 software. The data were analyzed using t-test. *p < 0.05, **p < 0.01, *p < 0.05 indicates that the data difference is statistically significant.

[0056] Figure 2A is a bright field photograph of intestinal organoids in each group on the fifth day after administration of 5-hydroxy-3-indoleacetic acid to organoids in normal physiological state; Figure 2 B is the statistical graph of the germination rate of intestinal organoids in each group on the fifth day of 5-hydroxy-3-indoleacetic acid administration; Figure 2 C is the statistical graph of the crypt areas of intestinal organoids in each group on the fifth day of 5-hydroxy-3-indoleacetic acid administration.

[0057] Depend on Figure 2 It can be seen that in the experiment of 5-hydroxy-3-indoleacetic acid administration on organoids under normal physiological conditions, compared with the control group, the colon organoids in the 50μM 5-hydroxy-3-indoleacetic acid administration group showed significant improvements in organoid budding rate and organoid crypt domain (**p<0.01, *p<0.05), indicating that 5-hydroxy-3-indoleacetic acid can enhance the proliferation and differentiation ability of stem cells under normal physiological conditions.

[0058] Example 2 Effects of 5-hydroxy-3-indoleacetic acid on intestinal organoids under pathological conditions

[0059] In order to verify the repair effect of 5-hydroxy-3-indoleacetic acid on the proliferation and differentiation of damaged stem cells, this embodiment uses a gene defect to induce mice with impaired proliferation and differentiation of intestinal stem cells to simulate the pathological state of stem cells and establish a colon organoid model. It is reported that there is a close connection between the Gpr35 gene and intestinal stem cells, which plays an important regulatory role in the proliferation, differentiation and microenvironment maintenance of intestinal stem cells. Knocking out the Gpr35 gene will cause the proliferation and differentiation function of intestinal stem cells to be impaired. Therefore, this embodiment uses Gpr35 gene-deficient mice to extract colon crypt stem cells under pathological conditions, establish a colon organoid model simulating the pathological state of damaged stem cells, and administer 5-hydroxy-3-indoleacetic acid after primary cell passage. On the fifth day after administration, bright field photography was performed to count the budding rate and crypt domain indicators of the organoids, and detect the repair effect of 5-hydroxy-3-indoleacetic acid on the damaged stem cell proliferation and differentiation function.

[0060] (1) Experimental Materials

[0061] Mice: C57BL / 6J mice (female, 8 weeks old, genotype: Gpr35 fl / fl,Villincre+ ), 18-22 g, purchased from Nanjing Jicui Yaokang Experimental Animal Co., Ltd.

[0062] The remaining experimental materials are the same as those in Example 1.

[0063] (2) Solution preparation

[0064] Same as step (2) in Example 1.

[0065] (3) Extraction of colonic crypt stem cells under pathological conditions

[0066] The genotype was Gpr35 fl / fl,Villincre+ The mice were killed by cervical dislocation, and the abdominal cavity was opened. The colon was removed and placed in a 90 mm culture dish. The colon was washed with ice HBSS buffer, and the fat, mucosa and connective tissue on the intestine were scraped off with a sterilized slide. After washing, the intestinal segment was cut longitudinally. After further washing, the intestinal segment was transferred to a 50 mL centrifuge tube containing ice HBSS buffer. After vigorous vortexing for 5 minutes, the intestinal segment was transferred to a 90 mm culture dish containing ice HBSS buffer and washed again twice. The intestinal segment was transferred to a 35 mm culture dish, and the colon was cut into small segments (<1 mm) with scissors. 2 ), add 3mL collagenase solution, and suspend the colon tissue fragments in the solution. Place the culture dish in a 37℃ cell culture incubator and incubate it. Use a 1mL pipette to blow several times every 10min, and then check under a microscope whether the single epithelial unit (crypt) is separated and detached from the tissue (this step takes about 40-60min, until most of the crypts are separated). Pass the collagenase solution containing tissue fragments through a 70μm cell filter and wash the filter with 9mL washing solution. Collect the filtrate and transfer it to a 15mL centrifuge tube. Centrifuge it at 80g at room temperature for 5min with a low-temperature high-speed centrifuge, then discard the supernatant with a pipette, and resuspend the precipitate with 1mL washing solution to obtain the extracted crypt stem cell suspension.

[0067] (4) Culture of colon organoids

[0068] Same as step (4) of Example 1.

[0069] (5) Subculture of colon organoids

[0070] Same as step (5) of Example 1.

[0071] (6) 5-Hydroxy-3-indoleacetic acid administration experiment in colon organoids

[0072] Same as step (6) of Example 1.

[0073] The experimental data are expressed as Mean ± SEM, and the results were analyzed and processed using GraphPad Prism 8 software. The data were analyzed using t-test. *p < 0.05, **p < 0.01, *p < 0.05 indicates that the data difference is statistically significant.

[0074] Figure 3 A is a bright field photograph of intestinal organoids in each group on the fifth day after administration of 5-hydroxy-3-indoleacetic acid to organoids simulating pathological conditions; Figure 3 B is the statistical graph of the germination rate of intestinal organoids in each group on the fifth day of 5-hydroxy-3-indoleacetic acid administration; Figure 3 C is the statistical graph of the crypt areas of intestinal organoids in each group on the fifth day of 5-hydroxy-3-indoleacetic acid administration.

[0075] Depend on Figure 3 It can be seen that in the experiment of administering 5-hydroxy-3-indoleacetic acid to organoids under pathological conditions with impaired stem cell function, compared with the control group, the budding rate and crypt area of ​​the colon organoids in the 50μM 5-hydroxy-3-indoleacetic acid administration group were significantly increased (**p<0.01, *p<0.05), indicating that 5-hydroxy-3-indoleacetic acid can improve the ability of functionally impaired stem cells to proliferate and differentiate, that is, it has the effect of promoting stem cell repair.

[0076] As described above, although the present invention has been shown and described with reference to specific preferred embodiments, it should not be construed as limiting the present invention itself. Various changes in form and details may be made without departing from the spirit and scope of the present invention as defined in the appended claims.

Claims

1. Use of tryptophan metabolites in the preparation of drugs for promoting stem cell repair, characterized in that: The tryptophan metabolite is 5-hydroxy-3-indoleacetic acid.

2. Use of tryptophan metabolites in the preparation of stem cell culture medium additives, characterized in that: The tryptophan metabolite is 5-hydroxy-3-indoleacetic acid.

3. The use according to claim 1 or 2, characterized in that: The medicine comprises 5-hydroxy-3-indoleacetic acid or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable adjuvant.

4. The use according to claim 3, characterized in that: The auxiliary materials include one or more of emulsifiers, adhesives, diluents, wetting agents, antioxidants, lubricants, solubilizers, preservatives or disintegrants.

5. The use according to claim 1 or 2, characterized in that: The effective dose of 5-hydroxy-3-indoleacetic acid in the drug is 50 μM.

6. The use according to claim 1 or 2, characterized in that: The dosage form of the drug is tablet, granule, oral solution, capsule, pill, emulsion, suspension, injection, ointment, spray or patch.

7. The use according to claim 1 or 2, characterized in that: The administration route of the drug is oral administration, enema administration or injection administration.

8. The use according to claim 1 or 2, characterized in that: The 5-hydroxy-3-indoleacetic acid enhances the proliferation and differentiation ability of stem cells under normal physiological conditions.

9. The use according to claim 1 or 2, characterized in that: The 5-hydroxy-3-indoleacetic acid improves the proliferation and differentiation capabilities of functionally impaired stem cells.

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