CN114107185A - Pharmaceutical composition for treating Crohn's disease and preparation method thereof - Google Patents
Pharmaceutical composition for treating Crohn's disease and preparation method thereof Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
- C12N5/0662—Stem cells
- C12N5/0668—Mesenchymal stem cells from other natural sources
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2509/00—Methods for the dissociation of cells, e.g. specific use of enzymes
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Abstract
The invention discloses a pharmaceutical composition for treating Crohn's disease and a preparation method thereof, wherein the pharmaceutical composition comprises umbilical cord mesenchymal stem cells and a pharmaceutically acceptable carrier. The umbilical cord mesenchymal stem cells are easy to obtain and amplify, have no immunogenicity, have the functions of immunoregulation and tissue repair, and can promote CD healing. The umbilical cord mesenchymal stem cells prepared by the method have strong potential of immunoregulation and immunosuppression, have extremely low immunogenicity, and have no foreign body rejection in clinical application.
Description
Technical Field
The invention relates to the field of medicines, in particular to a pharmaceutical composition for treating Crohn's disease and a preparation method thereof.
Background
Crohn's Disease (CD) is a chronic inflammatory granulomatous disease of the gastrointestinal tract whose etiology is not yet well understood, the pathogenesis is very complex, influenced by genetic susceptibility, congenital and adaptive immune system disorders, environmental factors and intestinal microbiota, the peak age of onset is 18-35 years, men are slightly older than women (1.5: 1). The pathological changes can affect any part of the digestive tract, are mostly seen in the terminal ileum and the adjacent colon, are distributed in a segmental or jumping way, the invasion depth can reach the whole layer of the intestinal wall, the intestinal wall is thickened and fiberized due to repeated chronic inflammation, the intestinal cavity is narrow, the clinical characteristics comprise abdominal pain, diarrhea, the decline of the physique, abdominal mass, fistula formation and intestinal obstruction, the pathological changes can be accompanied with the general manifestations of fever and the like and the external damage of joints, skin, eyes, oral mucosa and the like, and the common complications are as follows: intestinal stenosis, obstruction, abdominal abscess, fistula, perianal lesion and the like have a tendency of recurrence for the whole life, severe patients are delayed and not healed, and the life quality is seriously influenced.
The therapeutic goal of CD is mainly to induce and maintain remission, but there are no specific drugs for CD so far, and currently applied drug therapy is mainly through modulation of inflammation and immune response, such as 5-aminosalicylic acid (5-AsA), hormones, immunosuppressants, biological agents, etc., and some patients even need surgical treatment. Although the medicine and the surgical treatment can relieve the state of the Crohn's disease and achieve a certain curative effect, the long-term use still has serious risks of secondary failure, high recurrence and multiple complications, even teratogenesis, tumors and the like, the life quality of patients cannot be fully improved, the patients need to bear long-term disease affliction and economic burden, and the treatment and the realization of long-term healing of the patients still face important challenges of clinicians. Thus, there is a need for new, safer, and effective treatments to alleviate symptoms of disease for long periods of time, effectively controlling disease progression.
At present, research on the treatment of Crohn's disease by MSCs has progressed to a certain extent, and two types of adipose mesenchymal stem cells and bone marrow mesenchymal stem cells are mainly used. However, fat or bone marrow MSCs are easily rejected and poorly tolerated.
Disclosure of Invention
The invention aims to provide a pharmaceutical composition for treating Crohn's disease, which has good rejection resistance and tolerance.
The invention also aims to provide a preparation method of the pharmaceutical composition.
In order to achieve the above purpose, the invention provides the following technical scheme:
a pharmaceutical composition for treating crohn's disease, comprising umbilical cord mesenchymal stem cells and a pharmaceutically acceptable carrier.
Numerous experimental studies show that, compared with adipose or bone marrow MSCs, the umbilical cord mesenchymal stem cells have more excellent immunoregulation and immunosuppression potential, and are very suitable for treating moderate and severe Crohn's disease; and the umbilical cord mesenchymal stem cells can reduce rejection and tolerance in the preparation process of the autologous MSCs during treatment. This is due to its low expression of the histocompatibility complex MHC-I and no expression of MHC-II, CD40, CD80, CD86, so that immunogenicity is very low and foreign rejection symptoms are hardly produced.
Preferably, the umbilical cord mesenchymal stem cells are passage 5 umbilical cord mesenchymal stem cells. The hUCMSCs can be stably passaged to the 9 th generation, but the cells are gradually reduced in the stationary phase of G0/G1 and gradually increased in the (S + G2/M) phase with the increase of the number of passages, which shows that the proliferation capacity and the differentiation potential of the cells are reduced with the increase of the number of passages. But the hUCMSCs of the 3 rd to 6 th generations have stable proliferation conditions, and the cell growth curves are all in an S shape. The surface marker of the stem cell has no obvious expression reduction along with the increase of the passage times; wherein the expression level of the hUCMSCs hematopoietic line cell marker in the 1 st-5 th generation is gradually reduced along with the number of passages. The cells are adopted as tissue engineering seed cells, which are suitable for an amplification algebra, can ensure enough cell number and can keep the optimal differentiation capacity of the cells.
Preferably, the pharmaceutical composition is in the form of injection.
Preferably, the carrier is a physiological saline solution containing albumin in a volume fraction of 5%. It was found that the injection of saline with a volume fraction of 5% albumin was more effective in treating moderate to severe crohn's disease.
Preferably, the pharmaceutical composition contains 10mL of physiological saline per 100mL of the pharmaceutical composition.
The preparation method of the pharmaceutical composition for treating Crohn's disease comprises the preparation of umbilical cord mesenchymal stem cells.
Preferably, the preparation method of the umbilical cord mesenchymal stem cells comprises the following steps:
ligating two ends of fresh umbilical cord tissue, soaking, cleaning, sterilizing, placing into normal saline, cutting umbilical cord into 3-4cm segments, and washing off blood; cleaning umbilical cord, adding normal saline, removing umbilical vein and umbilical artery, and cutting into 1-2mm pieces3The fine tissue blocks are put into a culture bottle;
placing the culture flask at 37 deg.C and 5% CO2Culturing in an incubator for 4-6h, adding a serum-free MSC culture medium, changing the culture medium once every 3 days, culturing until the cells climb out, digesting with Tryple-Express, passaging, freezing, and completing the corresponding detection items in the 3 rd generation; digesting the subcultured cells, culturing and proliferating to the 5 th generation, and digesting by a digestive juice to prepare a single cell suspension;
washing the cells with PBS containing 3% serum albumin by volume fraction, and incubating with monoclonal antibodies of CD14-PE, CD34-PE, CD45-PE, CD73-PE, CD90-PE, CD105-PE and HLA-DR-PE respectively for 15min at room temperature in dark; washing cells with PBS, centrifuging, and removing supernatant; according to the expression ratio of CD73/CD90/CD105, 5 th generation cells, namely the umbilical cord mesenchymal stem cells, with the positive rate of more than 99% and the expression rate of HLA-DR/CD34CD45 of less than 1% are screened.
Preferably, the soaking, cleaning and disinfecting specifically comprises: soaking the umbilical cords with the two ends tied up in normal saline for cleaning, and then spraying with alcohol; then the umbilical cord is washed 2-3 times with physiological saline.
The umbilical cord adopted by the application is derived from a bifurcation in the process of parturition, has the characteristics of wide source, convenient material acquisition and no limitation of ethics, and obtains stable and high-quality umbilical cord mesenchymal stem cells through technical innovation of special steps of acquisition, separation, amplification and the like, thereby reducing the production and treatment cost, further shortening the treatment process and providing a better scheme for the research and development of medicaments for treating the Crohn disease.
An application of umbilical cord mesenchymal stem cells in preparing a pharmaceutical composition for treating moderate and severe Crohn's disease.
Preferably, the pharmaceutical composition is prepared in the form of an injection.
Preferably, the pharmaceutical composition is administered by a combination of a sub-mucosal enteromirror injection and a systemic intravenous drip.
Preferably, the pharmaceutical composition is injected to a site of a submucosal lesion of an enteroscope.
Preferably, the pharmaceutical composition is prepared from 393.7-6267.5 ten thousand umbilical cord mesenchymal stem cells/cm2Dose of ulcer submucosal injection combined with systemic intravenous injection of 100 ten thousand umbilical cord mesenchymal stem cells/kg body weight dose.
The CD treatment research in the prior art mostly adopts systemic intravenous drip or anal fistula intratubular injection, and the local submucosal injection of lesion part is combined with intravenous drip in the application, so that the angiogenesis near the lesion part is facilitated, the wound healing is promoted, the treatment effect can be obviously improved, and the occurrence of complications is reduced.
Has the advantages that: compared with the common bone marrow mesenchymal stem cells in the prior art, the umbilical cord mesenchymal stem cells have stronger immunosuppressive function; the method is more primitive and has stronger proliferation and differentiation capacities; and the immune cells are more immature, the functional activity is low, and the immune response and the graft-versus-host disease are not easy to trigger. Average 4X 10X per cm of umbilical cord tissue5The stem cells, viruses, bacteria and the like are difficult to permeate the placenta barrier, so that the probability of the pollution of components in the umbilical cord blood is lower than that of other stem cells.
The umbilical cord mesenchymal stem cells are easy to obtain and amplify, have no immunogenicity, have the immunoregulation and tissue repair capacity, and can promote CD healing. The umbilical cord mesenchymal stem cells prepared by the method have strong potential of immunoregulation and immunosuppression, have extremely low immunogenicity, and have no foreign body rejection in clinical application.
It should be understood that all combinations of the foregoing concepts and additional concepts described in greater detail below can be considered as part of the inventive subject matter of this disclosure unless such concepts are mutually inconsistent.
Drawings
FIG. 1 is a graph showing the change in body weight of rats.
FIG. 2 is a graph showing the change of disease activity index in rats.
FIG. 3 shows the general appearance of the small intestine and colon before and after treatment in rats.
FIG. 4 is a graph of gross injury scores for rat colon.
FIG. 5 is an optical microscope photograph of rat colon tissue.
Figure 6 is a histological scoring of rat colitis.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the following description will clearly and completely describe the embodiments of the present invention in conjunction with the technical solutions. It is to be understood that the embodiments described are only a few embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the described embodiments of the invention without any inventive step, are within the scope of protection of the invention. Unless defined otherwise, technical or scientific terms used herein shall have the ordinary meaning as understood by one of ordinary skill in the art to which this invention belongs.
The proportions not described in the present specification are mass ratios.
Example 1
An injection for treating moderate-severe Crohn's disease comprises umbilical cord mesenchymal stem cells and physiological saline containing 5% (volume fraction) of albumin.
The extraction method of the umbilical cord mesenchymal stem cells comprises the following steps: ligating two ends of fresh umbilical cord tissue, soaking in a sterile bottle containing normal saline, and transporting to a laboratory at 2-8 deg.C; opening the bottle in an ultraclean working counter, discarding the preservation solution in the bottle, adding physiological saline (only by immersing umbilical cord) into the bottle, and washing by shaking. After discarding the saline, the umbilical cord was poured into a sterile 100mm petri dish and the surface of the umbilical cord was sprayed with a 75% ethanol solution. Cleaning the umbilical cord sprayed with alcohol with normal saline for 2-3 times, adding normal saline into a culture dish, dividing the umbilical cord into 3-4cm segments with sterile scissors, and washing off blood; putting the cleaned umbilical cord into a sterile 100mm culture dish containing normal saline, removing umbilical vein and umbilical artery, separating Fahrenheit glue, and cutting the separated tissue blocks with sterile scissors; after cutting, the tissue was evenly spread in T75 cell culture flasks. After culturing T75 in an incubator for 2-3h, 6mL serum-free MSC medium (purchased from Shanghai Cynomorium Biotech, Inc.) was added. Changing the liquid once every 3 days, observing the cell creeping-out condition by a microscope after 7-12 days, and digesting and passaging by using digestive juice after the cells are densely paved around the tissue block.
Culturing the cells which are proliferated to the 5 th generation, and digesting the cells by using digestive juice to prepare single cell suspension. The cells were washed with PBS containing 3% serum albumin by volume fraction and incubated with monoclonal antibodies to CD14-PE, CD34-PE, CD45-PE, CD73-PE, CD90-PE, CD105-PE and HLA-DR-PE, respectively, for 15min at room temperature in the dark. The cells were washed with PBS, centrifuged, and the supernatant discarded. Adding 0.2mL of PBS containing 10g/L of paraformaldehyde, determining a background marker by using an isotype control monoclonal antibody, and analyzing the marked cells by a flow cytometer to obtain the purity and type parameters of the cells. According to the expression ratio of CD73/CD90/CD105, P5 generation cells with the positive rate of more than 95% are screened out and stored in a warehouse, and meanwhile, the expression rate of HLA-DR/CD34/CD11/CD19/CD45 is required to be lower than 2% (preferably lower than 1%), so that the umbilical cord mesenchymal stem cells are obtained.
Example 2
Animal experiments:
1. the experimental method comprises the following steps:
30 female Sprague-Dawley rats (6-8 weeks) of specific pathogen free grade (SPF) purchased from Shanghai Si Rick laboratory animals Ltd, acclimatized for one week prior to the experiment, under the following conditions: temperature 22 + -2 deg.C, humidity 55 + -5%, and normal diet. D0 days after fasting without water prohibition for 24h, the food was randomly divided into three groups (n is 10/group): control group (control), trinitrobenzenesulfonic acid (TNBS) group, TNBS + stem cell group.
On day D1, all rats were anesthetized by intraperitoneal injection of 1ml/kg body weight of 3% sodium pentobarbital.
TNBS group: mixing 5% TNBS and absolute ethyl alcohol according to a volume ratio of 1:1 to prepare a 50% ethanol solution containing 2.5mg/ml TNBS, performing enema at a position 8-10cm away from an anus according to the standard of 100mg/kg of body weight of the mixed solution, pulling out a hose after filling, keeping a rat head upside down for about 30s, and ensuring that the mixed solution reaches the whole colon;
TNBS + stem cell group: 1X 10 administration 12h after TNBS enema administration6Kg. weight (body weight) hUC-MSC2ml suspension for tail vein injection;
control group (control): an enema with 50% ethanol of the same volume was given, and 2ml of physiological saline was given into the tail vein after the enema was given 12 hours.
After the model building is completed, the rats are laid down to be awake, are raised in an SPF level environment, are fed with normal diet, observe the mental state, the eating, the activity, the stool character and the like every day, and record the body weight. Feces were taken daily for occult blood tests. D8 Gastrodia elata was used to kill the mice, and the colon tissue of the mice was collected to observe the pathological changes.
2. Grading standard:
A. assessment of Disease Activity Index (The Disease Activity Index orders, DAI): the change of the body weight of the rat is recorded every day, the stool character is observed, the stool occult blood is detected, and DAI scoring is carried out according to the standard formulated by Murthy and the like, wherein the scoring standard is shown in a table 1.
TABLE 1 rat TNBS colitis DAI score criteria
Dai ═ (weight loss score + stool trait score + hematochezia score)/3
b. Normal feces: shaped granular feces
c. Sparse feces: pasty feces not sticking to anus
d. Diarrhea: water-like stool stuck on anus
B. Assessment of Colon gross injury score (Colon Macroscopic Damage Index, CMDI): the materials were collected by visual observation for no damage, congestion, edema and ulcer of the intestinal mucosa, and the colon was scored roughly, the scoring criteria are shown in Table 2.
TABLE 2 Colon gross lesions Scoring criteria
C. Histological Score (HPS): the colon histopathological section is subjected to conventional HE staining, and the infiltration degree of the colon leucocytes, the goblet cell morphology, the blood vessel density and the intestinal wall thickness are observed under an optical microscope to be subjected to histological scoring, wherein the scoring standard is shown in a table 3.
TABLE 3 colitis histology score
3. The experimental results are as follows:
FIG. 1 shows the weight change of rats after TNBS modeling and stem cell therapy, with time on the abscissa and mouse weight on the ordinate. Compared with the control group, the TNBS group body weight is gradually reduced, while the TNBS + stem cell group body weight is relatively stable and is not obviously reduced.
FIG. 2 shows the disease activity index change of rats after TNBS modeling and stem cell therapy, with time on the abscissa and Disease Activity Index (DAI) on the ordinate. Compared with a control group, the disease activity index of the TNBS group rat is obviously increased, and the disease activity index of the rat after the stem cell enema is used has a descending trend.
Fig. 3 shows the general appearance of small intestine and colon of rat after TNBS modeling and stem cell treatment, the left image is before treatment, and the right image is after treatment. Compared with a control group, the TNBS group rat colon and peripheral tissues and organs are obviously adhered and are not easy to separate, obvious congestion, edema, hemorrhage, erosion and ulcer formation can be seen after the colon is cut open, necrosis can be seen in serious cases, the intestinal wall is obviously thickened, and the effect is better after stem cell treatment.
Fig. 4 is a graph of gross lesions in rat colon scored according to the CDMI scoring system, showing that the TNBS group rat CDMI score was significantly higher than the control group. Whereas the CDMI score decreased significantly after treatment with stem cells.
FIG. 5 is an optical microscope photograph of rat colon tissue. As can be seen from the figure, the rats in the control group have damage and deletion of colon mucosal epithelium, the arrangement of the inherent layer glands is basically normal, and a little lymphocyte, monocyte and neutrophil infiltration are seen in the mucosa and the submucosa; the TNBS group rats have lesions, deletions, erosion and ulcer on the colonic mucosa epithelium, the deformation, disorganization and even disappearance of the inherent glands, and the infiltration of densely distributed lymphocytes, monocytes and neutrophils is seen in the mucosa and the submucosa; compared with the TNBS group, the TNBS + stem cell treatment group has the advantages that the injury, deletion, erosion and ulcer degree of the colon mucosal epithelium are reduced, the number of the glands in the inherent layer is increased, the arrangement is close to normal, and the infiltration of lymphocytes, monocytes and neutrophils in the mucosa and the submucosa is reduced.
Figure 6 is a histological score for colitis in rats, with the TNBS group showing a significant increase in HPS score compared to the control group, and a decrease in HPS score after TNBS + stem cell treatment.
Example 3
Crohn's disease is treated with different injection modalities and dosages.
Screening patients with Crohn's disease, randomly dividing into five groups, and observing the effectiveness and safety of clinical remission of moderate and severe Crohn's disease by adopting different medicines and administration modes for 4 persons in each group.
Inclusion criteria for the subject were as follows:
1) in randomization, subjects aged between 18-75 years (inclusive) are considered to be of any age, male or female,
2) upon randomization, subjects who have been diagnosed with ileal, colonic or ileocecal crohn's disease for at least 3 months are recorded.
3) At present, the Crohn's disease is suffered and the score of the Crohn's Disease Activity Index (CDAI) is more than or equal to 220 and less than or equal to 450.
4) Endoscopy for active disease in the screening phase confirmed the presence of evidence of active inflammation and ulceration in the subject.
5) The subject must be free of active, latent or inadequately treated mycobacterium tuberculosis infection.
6) All women and all men with childbearing potential must be willing to use at least one efficient method of contraception from the time of signing an informed consent and throughout the study period until the 1 month post study drug administration.
7) Subjects who are willing and able to have been taken from a planning visit and treatment plan, laboratory examinations, and other research procedures.
8) Informed consent (and date noted) can be signed, indicating that the subject has been informed of all relevant parts of the study.
9) Subjects receiving non-forbidden combination therapy for any reason must maintain a stable treatment regimen, defined as no treatment or no dose alteration of stem cells given 7 days or 5 half-lives (whichever is longer) prior to the first injection of stem cells.
The following indices were observed at weeks 1, 4, 12, and 24, respectively:
1) crohn's Disease Activity Index (CDAI).
2) Reduced endoscopic scoring for Crohn's disease (SES-CD)
The following are the detection results of one group:
the result shows that the invention has good treatment effect and high safety, and 393.7-6267.5 ten thousand/cm2The MSC colon lesion submucosal injection and 100 ten thousand per kg body weight intravenous injection treatment can effectively improve the CDAI score and endoscopic SES-CD score of a moderate-severe CD patient and promote the healing of intestinal ulcer. And experiments show that the inflammation indexes CRP and the calprotectin of the patient do not change obviously.
The umbilical cord mesenchymal stem cells realize wound healing and tissue repair mainly by promoting epithelialization, granulation tissue and angiogenesis, and relate to multiple mechanisms: firstly, umbilical cord mesenchymal stem cells can promote the cells to 'home' to intestinal inflammatory tissues through the activation of IFN-gamma, IL-1 beta and the like and the coating of vascular cell adhesion molecule antibodies; the cell can also be used as a signal for regulating migration by expressing growth factors, such as vascular endothelial growth factor, platelet growth factor and the like and by the interaction between chemokines and CC chemokine receptors, and selectively migrates to injury and inflammation parts such as intestinal lamina propria, muscular layer, submucosa, mesenteric lymph node and the like to play a role; meanwhile, umbilical cord mesenchymal stem cells can also secrete adhesion molecules (intercellular adhesion molecules, vascular cell adhesion molecules and the like) and integrins which are involved in migration of inflammatory immune cells, so that migration of umbilical cord mesenchymal stem cells to intestinal inflammatory tissues is promoted. Secondly, the umbilical cord mesenchymal stem cells migrating to the inflammation part promote recruitment of macrophages and fibroblasts to the inflammation part by secreting vascular endothelial growth factor, keratinocyte growth factor, insulin-like growth factor and angiotensin-1, so that angiogenesis and collagen regeneration effects are generated, and survival and function recovery of local damaged tissue cells are stimulated; finally, umbilical cord mesenchymal stem cells can be differentiated into different types of mesenchymal cells in the intestinal inflammatory tissues, smooth muscle actin expression is improved, and damaged tissue repair is promoted.
Although the present invention has been described with reference to the preferred embodiments, it is not intended to be limited thereto. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the invention. Therefore, the protection scope of the present invention should be determined by the appended claims.
Claims (7)
1. A pharmaceutical composition for treating crohn's disease, comprising umbilical cord mesenchymal stem cells and a pharmaceutically acceptable carrier.
2. The pharmaceutical composition for treating crohn's disease according to claim 1, wherein the umbilical cord mesenchymal stem cells are passage 5 umbilical cord mesenchymal stem cells.
3. The pharmaceutical composition for treating crohn's disease according to claim 1, wherein the pharmaceutical composition is in the form of an injection.
4. The pharmaceutical composition for the treatment of crohn's disease according to claim 1, wherein the carrier is saline containing albumin in a volume fraction of 5%.
5. The pharmaceutical composition for treating Crohn's disease according to claim 4, wherein 10mL of physiological saline is contained per 100mL of the pharmaceutical composition.
6. The method for preparing the pharmaceutical composition according to claim 1, wherein the method for preparing the umbilical cord mesenchymal stem cells comprises the following steps:
ligating two ends of fresh umbilical cord tissue, soaking, cleaning, sterilizing, placing into normal saline, cutting umbilical cord into 3-4cm segments, and washing off blood; cleaning umbilical cord, adding normal saline, removing umbilical vein and umbilical artery, and cutting into 1-2mm pieces3The fine tissue blocks are put into a culture bottle;
placing the culture flask at 37 deg.C and 5% CO2Culturing in an incubator for 4-6h, adding a serum-free MSC culture medium, changing the culture medium once every 3 days, culturing until the cells climb out, digesting with Tryple-Express, passaging, freezing, and completing the corresponding detection items in the 3 rd generation; digesting the subcultured cells, culturing and proliferating to the 5 th generation, and digesting by a digestive juice to prepare a single cell suspension;
washing the cells with PBS containing 3% serum albumin by volume fraction, and incubating with monoclonal antibodies of CD14-PE, CD34-PE, CD45-PE, CD73-PE, CD90-PE, CD105-PE and HLA-DR-PE respectively for 15min at room temperature in dark; washing cells with PBS, centrifuging, and removing supernatant; according to the expression ratio of CD73/CD90/CD105, 5 th generation cells, namely the umbilical cord mesenchymal stem cells, with the positive rate of more than 99% and the expression rate of HLA-DR/CD34CD45 of less than 1% are screened.
7. The method for preparing the pharmaceutical composition according to claim 6, wherein the soaking, cleaning and disinfecting specifically comprises: soaking the umbilical cords with the two ends tied up in normal saline for cleaning, and then spraying with alcohol; then the umbilical cord is washed 2-3 times with physiological saline.
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Citations (3)
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| CN102920734A (en) * | 2012-11-14 | 2013-02-13 | 青岛奥克生物开发有限公司 | Mesenchymal stem cell injection and preparation method thereof as well as application in preparation of medicine for treating ulcerative colitis |
| CN104873542A (en) * | 2015-05-21 | 2015-09-02 | 北京青藤谷禧干细胞科技研究院有限公司 | Umbilical cord mesenchymal stem cell injection as well as preparation method and application thereof |
| CN110205287A (en) * | 2018-02-28 | 2019-09-06 | 清华大学 | A kind of cell preparation for treating inflammatory enteritis |
-
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102920734A (en) * | 2012-11-14 | 2013-02-13 | 青岛奥克生物开发有限公司 | Mesenchymal stem cell injection and preparation method thereof as well as application in preparation of medicine for treating ulcerative colitis |
| CN104873542A (en) * | 2015-05-21 | 2015-09-02 | 北京青藤谷禧干细胞科技研究院有限公司 | Umbilical cord mesenchymal stem cell injection as well as preparation method and application thereof |
| CN110205287A (en) * | 2018-02-28 | 2019-09-06 | 清华大学 | A kind of cell preparation for treating inflammatory enteritis |
Non-Patent Citations (2)
| Title |
|---|
| JIAN ZHANG等: "Umbilical Cord Mesenchymal Stem Cell Treatment for Crohn’s Disease: A Randomized Controlled Clinical Trial", 《GUT AND LIVER》, vol. 12, no. 1, pages 73 - 78, XP009545836, DOI: 10.5009/gnl17035 * |
| 陈继冰: "《干细胞临床应用》", 中山大学出版社, pages: 58 * |
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