KR101705378B1 - Composition for Preventing or Treating Graft-Versus-Host Disease Comprising Mesenchymal Stem Cell and IL-21 inhibitor - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating graft-versus-host disease comprising an IL-21 receptor expression-suppressing gene and mesenchymal stem cells as an active ingredient. According to the present invention, when IL-21 receptor-expressing gene and mesenchymal stem cell are used together to inhibit signal transduction of IL-21, expression of IL-21 receptor is decreased and signal transduction of IL-21 is blocked It has an effect of reducing graft-versus-host disease by inhibiting rejection of the host after grafting of the grafted bone marrow. In addition, such graft-versus-host disease reduction values have far-reaching effects compared with the case of treating mesenchymal stem cells alone. Therefore, the composition of the present invention having the above-mentioned effects can effectively inhibit the immune rejection reaction during the transplantation process and thus can be effectively used for preventing or treating graft-versus-host disease.

Description

TECHNICAL FIELD The present invention relates to a composition for preventing or treating a graft-versus-host disease comprising mesenchymal stem cells and Ⅰ L-21 blocker.

The present invention relates to a cell therapy agent capable of effectively preventing or treating immune diseases, and more particularly, to a cell therapy agent capable of effectively preventing or treating immune diseases, and more particularly, And a pharmaceutical composition for preventing or treating a host disease.

Graft-versus-host disease (GVHD) refers to a disease in which an immune response occurs by recognizing T lymphocytes in the peripheral blood or bone marrow of a donor that is injected at the time of allogeneic transplantation, . In other words, it is caused by live lymphocytes that have been transfused and the immune reaction causes symptoms such as liver dysfunction, skin lesion, jaundice, diarrhea, fever, and hemocytopenia. In severe cases, the patient may die.

Graft-versus-host disease (GVHD) is divided into acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD).

Chronic graft versus host disease usually occurs 4 to 6 months after transplantation, and rarely occurs 80 days before or 1 year after transplantation. Thus, it can be seen that homologous reactions are a prerequisite for chronic graft-versus-host disease, and that the onset of chronic graft versus host disease is long-latency or slow to affect target organs.

Acute Graft-versus-host disease is an important complication of allogeneic hematopoietic stem cell transplantation. It usually occurs within 30-40 days after allogeneic stem cell transplantation, invading the skin, liver and gastrointestinal tract. These acute graft-versus-host disease develops in three stages. In the first stage, it occurs before the bone marrow transplantation, and the tissue of the patient is damaged. In some cases, the antigen presenting cell is activated . In step 2, T cells in the transplanted bone marrow cells are activated. The antigen-presenting cells of an already activated patient differentiate T cells into Th1 cells, ultimately increasing the secretion of cytokines such as IL-2 and IFN-gamma. In the third stage, the organs of the patient are destroyed. When cytotoxic T cells and naturall killer cells are activated by cytokines secreted from activated Th1 cells, these cells attack the organs of the patient and cause graft-versus-host disease do.

Several methods have been proposed to treat such graft-versus-host disease. Methods for removing T cells from transplanted bone marrow cells, methods for administering antibodies against CD80, CD86, etc., and antibodies against cytokines such as IL-2 and IFN-gamma in order to inhibit the reaction between T cells and antigen presenting cells And the like. In addition, a method of administering a compound immunosuppressive agent such as cyclosporin A, rapamycin, FK-506 steroid preparation and the like is also used. Of these methods, compound immunosuppressant administration methods that inhibit activation of T cells have been most widely used.

Although many immunosuppressants have been developed to date, cyclosporine A has the most excellent clinical effects and is widely used for autoimmune diseases, rejection of organ transplantation, and various inflammatory diseases including acute graft versus host disease. It is recommended that cyclosporin be used at a low dose because it has the disadvantage that when it is used at a high dose, it completely inhibits the activation of T cells and treats the disease but it shows significant side effects including kidney toxicity.

Meanwhile, Mesenchymal Stem Cell (MSC) is a stem cell existing in the whole body including bone marrow that can differentiate into various cell lines such as adipocytes, bone cells and chondrocytes. Mesenchymal stem cells have been isolated from a number of species including humans, mice, rats, dogs, goats, rabbits and cats. Recently, it has been reported that mesenchymal stem cells inhibit various T lymphocyte activities in in vitro and in vivo and demonstrate immunoregulatory ability, and studies are being conducted to treat immune diseases by using them.

Korean Patent Publication No. 2011-0044490 discloses a technique for treating immune diseases using mesenchymal stem cells into which a nucleotide sequence encoding TGF-beta has been introduced. Korean Patent Publication No. 2008-0078204 discloses that when dendritic cells (DCs) are co-cultured with mesenchymal stem cells (MSCs), the immunosuppressive effect of dendritic cells is markedly increased, so that they can be used for immunosuppressive agents The contents are disclosed.

However, many techniques have not yet been developed for the treatment of immune diseases using mesenchymal stem cells. Therefore, it is required to develop new techniques for more effective therapeutic effect and safety in the body.

Therefore, the inventors of the present invention have been studying a method for preventing or treating graft-versus-host disease more effectively using mesenchymal stem cells, and it has been found that when a method of suppressing signal by IL-21 is treated with mesenchymal stem cell transplantation, The present inventors have completed the present invention by confirming that the anti-rejection reaction is effectively inhibited and the effect of reducing the symptoms of graft-versus-host disease is excellent.

Accordingly, it is an object of the present invention to provide a novel cell therapy composition capable of effectively inhibiting the immune rejection reaction occurring during the transplantation process and thereby improving the therapeutic effect. In particular, the present invention provides a novel cell therapy composition comprising mesenchymal stem cells and a gene And a pharmaceutical composition for preventing or treating graft-versus-host disease.

It is a further object of the present invention to provide a method of preventing or treating graft-versus-host disease induced by transplantation or transfusion using the composition of the present invention.

In order to accomplish the object of the present invention as described above, the present invention provides an immunodeficiency disease comprising an mesenchymal stem cell and an expression-suppressing gene for IL-21 (Interleukin-21) (siIL-21R vector DNA) Provides a pharmaceutical composition for the prevention or treatment of graft-versus-host disease.

In one embodiment of the present invention, the mesenchymal stem cells may be human-derived mesenchymal stem cells.

In one embodiment of the present invention, the IL-21 receptor expression-suppressing gene may have the amino acid sequence of SEQ ID NO: 1.

In one embodiment, the composition comprises a therapeutically effective amount of the IL-21 receptor expression inhibiting gene in an amount of 1 ug / ul to 3 ug / ul, and the mesenchymal stem cell is treated with a therapeutically effective amount of 2.5 mg / kg to 250 mg / kg.

In one embodiment of the present invention, the composition may be in a form for injection intended to be injected intravenously or intramuscularly into a patient.

Further, according to the present invention,

A method for preventing or treating graft-versus-host disease induced by transplantation or transfusion, comprising injecting mesenchymal stem cells into a mammal other than a human to which the transplantation recipient is to be administered, and injecting a gene for inhibiting the expression of a receptor for IL-21 . ≪ / RTI >

When the composition of the present invention is applied to an animal to which a bone marrow transplant recipient is applied, the IL-21 signaling mechanism is inhibited by inhibiting the expression of IL-21 receptor, thereby effectively reducing the immune rejection due to the signal, thereby preventing or preventing graft- It has a therapeutic effect. In addition, such graft-versus-host disease reduction values are significantly improved compared with the case of treating a mesenchymal stem cell group alone. Therefore, the composition of the present invention having the above-mentioned effects can effectively inhibit the immune rejection reaction during the transplantation process and thus can be effectively used for preventing or treating graft-versus-host disease.

FIG. 1 is a graph showing the effect of IL-21R shRNA and IL-21R shRNA on mesenchymal stem cells (MSC) and mesenchymal stem cells treated with IL-21 in an animal model of graft-versus- And the degree of the disease symptom according to the progression.

The present invention provides a composition for preventing or treating graft-versus-host disease comprising an inhibitor of receptor expression on IL-21 and mesenchymal stem cells as an active ingredient.

In particular, the present invention is characterized in that the mesenchymal stem cells and the receptor-suppressing gene for IL-21 are used together for the effective treatment of graft-versus-host disease. In general, IL-21 (IL-21) (IL-21R), a cytokine that is mainly produced by CD4 + T lymphocytes and exhibits homology to the subunit of IL-2 and IL-15 receptors and interacts with the receptor subunit γ- (Collins, 2003, Zhang, 2003). To date, such receptors have been observed in T cells and B cells, natural killer lymphocytes, monocytes, and dendritic cells.

In addition, signaling induced by the interaction between IL-21 and its receptor (IL-21R) is known to induce an immuno-inflammatory response, and in a number of studies performed on B cells, IL- Or murine cell death programs in murine cells (Mehta 2003, Jin 2004). In addition, human peripheral blood T lymphocytes produce a high level of interferon-gamma (IFN-gamma) indicating a Th1 response after IL-21 stimulation, whereas in some murine models IL-21 is expressed at a higher level in Th2 lymphocytes And promoted the differentiation of these cell types (Ma 2003, Wurstel 2002).

In addition, studies on animal carcinogenesis and diabetes models have demonstrated the ability of IL-21 to modulate the activity of T lymphocytes / natural killer cells and the production of cytokines, and the development of immune-inflammatory processes and sustained response (Gallegos et al., 2004). Thus, regulation of signal transduction between IL-21 and its receptors is emerging as a new therapeutic strategy for all immuno-inflammatory diseases characterized by production or activity of IL-21.

Accordingly, the present inventors have used a receptor-suppressing gene for IL-21 to effectively inhibit signal transduction between IL-21 and its receptor for the treatment of graft-versus-host disease caused by immunological rejection Respectively.

 The receptor-suppressing gene for the IL-21 used in the present invention is a gene capable of specifically inhibiting the expression of the IL-21 receptor gene by specifically targeting the IL-21 receptor gene.

Actually, the inventors of the present invention conducted the present invention in order to confirm whether treatment of the receptor-expressing gene for IL-21 with mesenchymal stem cells can treat the symptoms of graft-versus-host disease together with improvement and prevention. For example, mice were first induced to develop graft-versus-host disease and then treated with IL-21 receptor-expressing gene and mesenchymal stem cell-treated group and mesenchymal stem cell-treated group The results of the investigation of the symptoms of graft-versus-host disease show that treatment of mesenchymal stem cells with the receptor-expressing gene for IL-21 and mesenchymal stem cell treatment significantly improved the symptom severity (See Fig. 1).

Therefore, the inventors of the present invention have found that a composition comprising a receptor-suppressing gene for IL-21 and mesenchymal stem cells together can be used as a new therapeutic agent for graft-versus-host disease.

Therefore, the present invention provides a pharmaceutical composition for preventing or treating a graft-versus-host disease comprising an IL-21 receptor-expressing gene and mesenchymal stem cells as an active ingredient.

The IL-21 receptor expression-suppressing gene that can be used in the present invention is a gene capable of inhibiting the expression of IL-21 receptor by targeting IL-21 receptor, preferably a nucleotide sequence of SEQ ID NO: 1 It may be true.

In addition, the IL-21 receptor expression-suppressing gene according to the present invention may be injected into the body in the form of recombinant vector DNA comprising SEQ ID NO: 1.

In one embodiment of the present invention, vector DNA comprising the gene for inhibiting the expression of IL-21 receptor (siL-21R), that is, the DNA consisting of the nucleotide sequence of SEQ ID NO: 1, was injected into the body.

The gene for inhibiting the expression of the receptor for IL-21 of the present invention or a recombinant vector containing the same may be obtained chemically or by using a gene recombination technique.

In addition, the mesenchymal stem cells usable in the present invention may be mesenchymal stem cells of an animal, preferably mammalian cells, more preferably human mesenchymal stem cells. The mesenchymal stem cells of the present invention may be derived from bone marrow, adipose tissue, peripheral blood, liver, lung, amniotic fluid, placenta chorionic membrane or umbilical cord blood, and are particularly preferably derived from human adipocytes.

Although the mesenchymal stem cells are present in a very small amount in bone marrow and the like, the process of isolating and culturing the mesenchymal stem cells is well known in the art (for example, as disclosed in U.S. Patent No. 5,486,359) And then proliferating in the absence of differentiation ability after being separated from the hematopoietic stem cells of bone marrow by adhesion characteristics.

Specifically, the process for obtaining mesenchymal stem cells is as follows: (1) Separation of mesenchymal stem cells from a mammalian animal, preferably a human mesenchymal stem cell source such as blood or bone marrow, Step (said marrow can be extracted from tibia, femur, spinal cord or iliac bone); (2) culturing the isolated cells in a suitable medium; And (3) removing floating cells in the culture process and subculturing the cells attached to the culture plate, thereby obtaining finally formed mesenchymal stem cells.

As the medium used in the above process, any medium generally used for culturing stem cells can be used. Preferably, it is a medium containing serum (for example, fetal bovine serum, horse serum and human serum). Mediums which can be used in the present invention include, for example, RPMI series, Eagles ' s MEM (Eagle's minimum essential medium, Eagle, H. Science 130: Proc. Soc. Exp (1986)), 199 Iscove's MEM (Iscove, N. et al., J. Exp. Med. 1963), F12 (Ham, Proc. Natl. Acad < / RTI > Dulbecco's modification of Eagle's medium, Dulbecco, R. et al., Virology 8: 396 (1963)), F10 (Ham, RG Exp. Cell Res. 29: 515 (1959)), a mixture of DMEM and F12 (Barnes, D. et al., Anal. Biochem. 102: 255 (1980)), Way-mouth's MB752 / 1 (Waymouth, CJ Natl. Cancer Inst. 1959) and McCoy's 5A (McCoy, TA, et al., Proc. Soc. Exp. Biol. Med. )), But is not limited thereto. The medium may include other components such as antibiotics or antifungal agents (e.g., penicillin, streptomycin) and glutamine.

Identification of mesenchymal stem cells can be done by flow cytometry. Such flow cytometry analysis is carried out using a specific surface marker of mesenchymal stem cells. For example, since mesenchymal stem cells are positive for CD44, CD29 and / or MHC class I, mesenchymal stem cells can be verified.

In addition, the pharmaceutical composition of the present invention can be administered in appropriate formulations together with carriers and diluents known in the art and an inhibitory gene for the expression of receptor for IL-21 and mesenchymal stem cells, Parenteral administration, for example, intravenous injection, intramuscular injection, intraperitoneal injection, subcutaneous injection, suppository, and the like.

The formulations may be formulated with suitable excipients, fillers, binders, wetting agents, disintegrating agents, lubricants, surfactants, dispersants, buffers, preservatives, solubilizers, disinfectants, sweeteners, spices, analgesics, stabilizers, And the like.

The term " pharmaceutically acceptable " as used herein refers to a composition that is physiologically acceptable and does not normally cause an allergic reaction such as gastrointestinal disorder, dizziness, or the like when administered to humans. Specific examples of the carrier or the additive include water, a pharmaceutically acceptable organic solvent, collagen, polyvinyl alcohol, polyvinyl pyrrolidine, carboxyvinyl polymer, sodium alginate, water-soluble dextran, carboxymethyl sodium starch, pectin, , Gum arabic, casein, gelatin, agar, glycerol, propylene glycol, polyethylglycol, vaseline, paraffin, stearyl alcohol, stearic acid, human serum albumin, mannitol, sorbitol and lactic acid. One or more additives may be selected according to the form of preparation or may be combined as appropriate. Other pharmaceutically acceptable carriers can be found in Remington's Pharmaceutical Sciences, 19th ed., Mack Publishing Company, Easton, Pa., 1995).

In particular, since the composition according to the present invention includes cells such as mesenchymal stem cells, local administration to target cells can be performed in addition to conventional systemic administration such as intravenous administration and intraarterial administration, and catheter technique and surgical operation May be used.

In addition, the receptor-suppressing gene and mesenchymal stem cell of IL-21, which is an active ingredient of the pharmaceutical composition of the present invention, may be contained in a therapeutically effective amount. The " therapeutically effective amount " Refers to the amount of active ingredient or pharmaceutical composition that elicits a biological or medical response in a tissue, animal, or human that is physiologically or physiologically in origin by a physician or other clinician, . Thus, the optimal content can be readily determined by those skilled in the art and will vary with the type of disease, severity of the disease, the amount of other ingredients contained in the composition, the type of formulation, and the age, weight, general health status, sex and diet of the patient The time of administration, the route of administration and the rate of administration of the composition, the duration of the treatment, the drugs used concurrently, and the like. It is important to include the amount by which all of the above factors are taken into account so as to obtain the maximum effect in a minimal amount without side effects.

In view of this, the pharmaceutical composition according to the present invention may contain the IL-21 receptor-expressing gene at a concentration of 1 ug / ul to 3 ug / ul, and the mesenchymal stem cells may contain a therapeutically effective amount of 2 x 10 ⁵ cells to 2 x 10 ⁷ cells.

Further, the present invention provides a transplantation-transfusion-induced graft-versus-host disease, comprising the step of injecting the IL-21 receptor-expressing gene and the mesenchymal stem cell of SEQ ID NO: 1 into a mammal other than a human being recipient. Prevention or treatment of the disease.

In the method for preventing or treating graft-versus-host disease according to the present invention, it is possible to inject mammalian IL-21 receptor-expressing gene and mesenchymal stem cell into both, The stem cells can be first transplanted and the transgene can be injected intramuscularly with the IL-21 receptor expression-suppressing gene represented by SEQ ID NO: 1.

When the mesenchymal stem cells are injected first, the mesenchymal stem cells can be injected intravenously or intramuscularly.

Hereinafter, the present invention will be described in more detail with reference to Examples. It will be apparent to those skilled in the art that the following examples are merely illustrative of the present invention and that the scope of the present invention is not limited to these examples.

< Example  1>

IL -21 &lt; / RTI &gt; Mesenchymal stem cell  By treatment Graft-versus-host disease  Analysis of treatment effect

The present inventors have found that, in diseases caused by immune rejection such as graft-versus-host disease, mesenchymal stem cells and receptor-expressing genes for IL-21 are effective in treating these diseases, An animal model of the disease was constructed. We used a C57BL / 6 (H-2kb) mouse as a recipient and a bone marrow-reproductive precursor as a donor on the day of bone marrow transplantation. Bone marrow transplantation was performed by injecting bone marrow cells (5X10) and spleen cells (5X10) isolated from the donor mouse C57BL / 6 (H-2k / b) into the tail vein by 800 cGy irradiation with total body irradiation .

Mesenchymal stem cells to the mouse after 2 × 10 ⁶ cell amount by intravenous injection, and bone marrow transplantation after the first day and within (intra-muscle; im) the siIL-21R DNA vector muscle on day 3 of the pierced with 100ug / 50ul amount The clinical GVDH score was assessed by observing the progression of graft-versus-host disease (GVHD) on a daily basis to determine the weight change, posture, hair condition, activity level, Were assessed using the Clinical Scoring System, which scored each of the scores for the same parameters.

In this case, the siRNA IL-21R DNA vector introduction by the electric shock inhibits the expression of the IL-21 receptor gene by inhibiting IL-21R production in the cell, and the electric shock induces siRNA IL-21R DNA vector Lt; RTI ID = 0.0 &gt; IL-21 &lt; / RTI &gt; receptor gene. Therefore, this method can effectively inhibit the expression of IL-21R gene and block the immune response by IL-21.

As a result of the clinical evaluation, as shown in Fig. 1, the mice in which the IL-21 receptor-repressor gene and the mesenchymal stem cells were injected showed significantly reduced graft-versus-host disease symptoms compared to the control group injected with only mesenchymal stem cells Respectively. In addition, mice in all of these experimental groups showed similar weight changes.

Accordingly, the present inventors have found that when the IL-21 signal transduction inhibitor is treated with mesenchymal stem cell treatment, the symptoms of graft-versus-host disease can be effectively treated and treated.

The present invention has been described with reference to the preferred embodiments. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the present invention is defined by the appended claims rather than by the foregoing description, and all differences within the scope of equivalents thereof should be construed as being included in the present invention.

<110> Industry Academic Cooperation Foundation of Catholic University <120> Composition for Preventing or Treating Graft-Versus-Host Disease          Comprising Mesenchymal Stem Cell and IL-21 inhibitor <130> np11-1214 <160> 1 <170> Kopatentin 2.0 <210> 1 <211> 2937 <212> DNA <213> Artificial Sequence <220> <223> si IL-21 receptor vector sequence <400> 1 ggatcctttt ttgggaggta catgtccccc agcatagatc ttcaatattg gccattagcc 60 atattattca ttggttatat agcataaatc aatattggct attggccatt gcatacgttg 120 tatctatatc ataatatgta catttatatt ggctcatgtc caatatgacc gccatgttgg 180 cattgattat tgactagtta ttaatagtaa tcaattacgg ggtcattagt tcatagccca 240 tatatggagt tccgcgttac ataacttacg gtaaatggcc cgcctggctg accgcccaac 300 gacccccgcc cattgacgtc aataatgacg tatgttccca tagtaacgcc aatagggact 360 ttccattgac gtcaatgggt ggagtattta cggtaaactg cccacttggc agtacatcaa 420 gtgtatcata tgccaagtcc gccccctatt gacgtcaatg acggtaaatg gcccgcctgg 480 cattatgccc agtacatgac cttacgggac tttcctactt ggcagtacat ctacgrarra 540 gtcatcgcta ttaccatggt gatgcggttt tggcagtaca ccaatgggcg tggatagcgg 600 tttgactcac ggggatttcc aagtctccac cccattgacg tcaatgggag tttgttttgg 660 caccaaaatc aacgggactt tccaaaatgt cgtaacaact gcgatcgccc gccccgttga 720 cgcaaatggg cggtaggcgt gtacggtggg aggtctatat aagcagagct cgtttagtga 780 accgtcagat cactagaagc tttattgcgg tattttatca cagttaaatt gctaacgcag 840 tcagtgcttc tgacacaaca gtctcgaact taagctgcag tgactctctt aaggtagcct 900 tgcagaagtt ggtcgtgagg cactgggcag gtaagtatca aggttacaag acaggtttaa 960 ggagaccaat agaaactggg cttgtcgaga cagagaagac tcttgcgttt ctgataggca 1020 cctattggtc ttactgacat ccactttgcc tttctctcca caggtgtcca ctcccagttc 1080 aattacagct cttaaggcta gagtacttaa tacgactcac tataggctag cctcgacgcc 1140 accatgggat ggagctatat catcctcttt ttggtagcaa cagctacaga tgtccactcg 1200 caggggccgt gggggccatg ccgcgtggct gggccgcccc cttgctcctg ctgctgctcc 1260 agggaggctg gggctgcccc gacctcgtct gctacaccga ttacctccag acggtcatct 1320 gcatcctgga aatgtggaac ctccacccca gcacgctcac ccttacctgg caagaccagt 1380 atgaagagct gaaggacgag gccacctcct gcagcctcca caggtcggcc cacaatgcca 1440 cgcatgccac ctacacctgc cacatggatg tattccactt catggccgac gacattttca 1500 gtgtcaacat cacagaccag tctggcaact actcccagga gtgtggcagc tttctcctgg 1560 cggagagcat caagccggct ccccctttca acgtgactgt gaccttctca ggacagatta 1620 atatctcctg gcgctcagat tacgaagacc ctgccttcta catgctgaag ggcaagcttc 1680 agtatgagct gcagtacagg aaccggggag acccctgggc tgtgagtccg aggagaaagc 1740 tgatctcagt ggactcaaga agtgtctccc tcctccccct ggagttccgc aaagactcga 1800 gctatgagct gcaggtgcgg gcagggccca tgcctggctc ctcctaccag gggacctgga 1860 gtgaatggag tgacccggtc atctttcaga cccagtcaga ggagttaaag gaaggctgga 1920 accctcacct gctgcttctc ctcctgcttg tcatagtctt cattcctgcc ttctggagcc 1980 tgaagaccca tccattgtgg aggctatgga agaagatatg ggccgtcccc agccctgagc 2040 ggttcttcat gcccctgtac aagggctgca gcggagactt caagaaatgg gtgggtgcac 2100 ccttcactgg ctccagcctg gagctgggac cctggagccc agaggtgccc tccaccctgg 2160 aggtgtacag ctgccaccca ccacggagcc cggccaagag gctgcagctc acggagctac 2220 aagaaccagc agagctggtg gagtctgacg gtgtgcccaa gcccagcttc tggccgacag 2280 cccagaactc ggggggctca gcttacagtg aggagaggga tcggccatac ggcctggtgt 2340 ccattgacac agtgactgtg ctagatgcag aggggccatg cacctggccc tgcagctgtg 2400 aggatgacgg ctacccagcc ctggacctgg atgctggcct ggagcccagc ccaggcctag 2460 aggacccact cttggatgca gggaccacag tcctgtcctg tggctgtgtc tcagctggca 2520 gccctgggct aggagggccc ctgggaagcc tcctggacag actaaagcca ccccttgcag 2580 atggggagga ctgggctggg ggactgccct ggggtggccg gtcacctgga ggggtctcag 2640 agagtgaggc gggctcaccc ctggccggcc tggatatgga cacgtttgac agtggctttg 2700 tgggctctga ctgcagcagc cctgtggagt gtgacttcac cagccccggg gacgaaggac 2760 ccccccggag ctacctccgc cagtgggtgg tcattcctcc gccactttcg agccctggac 2820 cccaggccag ctaatgaggc tgactggatg tccagagctg gccaggccac tgggccctga 2880 gccagagaca agggagcgaa gctgatctct gaggaagacc tgaatagcgc cgtcgac 2937

Claims (7)

A pharmaceutical composition for preventing or treating a graft-versus-host disease comprising an IL-21 receptor-expressing gene and mesenchymal stem cell as an active ingredient,
The IL-21 receptor-expressing gene was contained at a concentration of 1 ug / ul to 3 ug / ul,
Wherein the mesenchymal stem cell comprises a therapeutically effective amount of 2 x 10 &lt; ⁵ &gt; cells to 2 x 10 &lt; ⁷ &gt; cells. The method according to claim 1,
Wherein said mesenchymal stem cells are human-derived mesenchymal stem cells. delete A method for preventing or treating graft-versus-host disease caused by transplantation or transfusion comprising the step of injecting an IL-21 receptor-expressing gene and mesenchymal stem cells of SEQ ID NO: 1 into a mammal other than a human being recipient ,
The IL-21 receptor-expressing gene was contained at a concentration of 1 ug / ul to 3 ug / ul,
Wherein the mesenchymal stem cells comprise a therapeutically effective amount of 2 x 10 &lt; ⁵ &gt; cells to 2 x 10 &lt; ⁷ &gt; cells. 5. The method of claim 4,
Wherein the IL-21 receptor-expressing gene is injected intramuscularly. delete 5. The method of claim 4,
Wherein said mesenchymal stem cells are injected by intravenous or intrathecal injection.

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