WO2020262916A1 - Composition pour le traitement d'une maladie artérielle périphérique - Google Patents

Composition pour le traitement d'une maladie artérielle périphérique Download PDF

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WO2020262916A1
WO2020262916A1 PCT/KR2020/008135 KR2020008135W WO2020262916A1 WO 2020262916 A1 WO2020262916 A1 WO 2020262916A1 KR 2020008135 W KR2020008135 W KR 2020008135W WO 2020262916 A1 WO2020262916 A1 WO 2020262916A1
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endothelial cells
human
cells
tooth
stem cells
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PCT/KR2020/008135
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English (en)
Korean (ko)
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주경민
남현
김충권
편희장
황지윤
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(주)메디노
성균관대학교산학협력단
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Priority claimed from KR1020200076924A external-priority patent/KR102397010B1/ko
Publication of WO2020262916A1 publication Critical patent/WO2020262916A1/fr

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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
    • A61K35/32—Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
    • 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
    • A61K35/44—Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the present invention relates to a composition for treatment of peripheral arterial disease, and more particularly, to a composition for preventing or treating peripheral arterial disease comprising tooth-derived stem cells and vascular endothelial cells as active ingredients.
  • Peripheral artery disease includes a wide range of vascular diseases caused by atherosclerotic, thromboembolic and inflammatory mechanisms that alter the structure and function of arteries.
  • peripheral arterial disease includes pulmonary thromboangiitis (thromboangiitis obliterans), obliterans, and critical limb ischemia, which are induced by vascular inflammation, thrombosis, hyperlipidemia, diabetes, etc.
  • thromboangiitis obliterans pulmonary thromboangiitis
  • obliterans obliterans
  • critical limb ischemia which are induced by vascular inflammation, thrombosis, hyperlipidemia, diabetes, etc.
  • peripheral arterial disease surgical operations such as stent implantation, balloon dilatation, angioplasty, or the use of drugs that expand blood vessels are mostly used, but this is to alleviate the primary symptoms, so it is not a fundamental treatment.
  • the only option is to take antisystemic analgesics to reduce pain, or to perform limb amputation to prevent the progression of gangrene or infection. Therefore, if there is a fundamental treatment method that can inhibit inflammation in blood vessels, inhibit muscle damage and fibrosis, and promote blood vessel formation, not only can various peripheral arterial diseases be effectively treated, but also limb amputation rate, mortality rate, etc. It is expected to be able to significantly lower the value.
  • a tooth-derived stem cell is a stem cell located in a tooth, and it is known that the tooth contains mesenchymal stem cells having a higher self-proliferative ability and differentiation ability than any other tissue at a high density. It is known that tooth-derived stem cells can be separated from gums such as pulp, periodontal ligaments, roots, dental pouches, and root papilla of indwelling or permanent teeth. In addition, it is not only possible to easily separate tooth-derived stem cells from naturally missing teeth or surgically removed teeth, but also its parents and grandparents as well as the owners of the teeth can be used in regenerative medicine, so its application value is very high. Therefore, in recent years, research on a method of using tooth-derived stem cells has been actively conducted (Korean Patent Registration No. 10-1715464).
  • the present invention was conceived to solve the problems of the prior art as described above, as a fundamental treatment method for peripheral arterial disease, a composition for preventing or treating peripheral arterial disease comprising tooth-derived stem cells and vascular endothelial cells as active ingredients Its purpose is to provide such as.
  • the present invention provides a pharmaceutical composition for preventing or treating peripheral arterial disease comprising tooth-derived stem cells and vascular endothelial cells as active ingredients.
  • the present invention provides a cell therapy for preventing or treating peripheral arterial disease, comprising tooth-derived stem cells and vascular endothelial cells as active ingredients.
  • the tooth-derived stem cells are preferably stem cells derived from pulp, periodontal ligaments, roots, dental vesicles, root papillae, gums, etc., more preferably pulp-derived stem cells.
  • the tooth-derived stem cells may not express one or more cell surface antigens selected from the group consisting of CD14, CD31, CD34, and CD45. However, it is not limited thereto as long as it is a stem cell capable of differentiating into adipocytes and bones derived from teeth.
  • the vascular endothelial cells are preferably Bend3 cells, human umbilical vein endothelial cells (HUVEC), human dermal microvascular endothelial cells (Human dermal microvascular). endothelial cells; HMVEC-D or HDMEC), human cardiac endothelial cells, human aortic endothelial cells (HAEC), human coronary and iliac artery endothelial cells; HIAEC or HCAEC), human cardiac microvascular endothelial cells, human bladder and uterine microvascular endothelial cells, human pulmonary artery endothelial cells; HPAEC or PASMC), human lung microvascular endothelial cells (HMVEC-L), human brachiocephalic artery endothelial cells (HBcAEC), human carotid artery endothelial cells (HCtAEC) , Human dermal lymphatic microvascular endothelial cells (HDLMVEC), human internal thoracic
  • vascular endothelial cells derived from stem cells including embryonic stem cells, mesenchymal stem cells, dedifferentiated stem cells, etc., or vascular endothelial cells produced by direct conversion of stem cells, etc.
  • stem cells including embryonic stem cells, mesenchymal stem cells, dedifferentiated stem cells, etc.
  • vascular endothelial cells produced by direct conversion of stem cells etc.
  • the tooth-derived stem cells and vascular endothelial cells may preferably be included in a number ratio of 1:0.1 to 1:10.
  • the peripheral arterial disease is preferably severe limb ischemia, obstructive thromboangiitis (thromboangiitis obliterans), arteriosclerosis obliterans, polyarteritis nodosa. (polyarteritis nodosa), etc., but is not limited to vascular diseases induced by vascular inflammation, thrombosis, hyperlipidemia, diabetes, etc. in all blood vessels except the central artery.
  • the present invention provides a method for preventing or treating peripheral arterial disease, comprising administering to an individual a composition comprising tooth-derived stem cells and vascular endothelial cells as active ingredients.
  • the present invention provides a use of a composition comprising tooth-derived stem cells and vascular endothelial cells as active ingredients to prevent or treat peripheral arterial disease.
  • the present invention provides a use for producing a medicament used in the treatment of peripheral arterial disease comprising tooth-derived stem cells and vascular endothelial cells as active ingredients.
  • compositions comprising tooth-derived stem cells and vascular endothelial cells according to the present invention as active ingredients to an animal model of peripheral arterial disease.
  • inflammatory reactions are suppressed, muscle damage is prevented, and fibrosis is inhibited from being induced.
  • the formation of new blood vessels can be promoted by increasing the ability to form blood vessels. Therefore, the composition of the present invention can be widely applied not only to the treatment of various peripheral arterial diseases caused by various causes such as atherosclerosis, thromboembolism, and inflammatory mechanisms, but also to alleviate primary symptoms by simply expanding blood vessels.
  • it can simultaneously treat various conditions of peripheral arterial disease, it is expected that it can be effectively used in the treatment of peripheral arterial disease by remarkably increasing treatment efficiency.
  • 1A is a view showing a result of confirming tooth-derived stem cells according to an embodiment of the present invention under an optical microscope.
  • 1B is a view showing a result of confirming the immune phenotype of tooth-derived stem cells according to an embodiment of the present invention by flow cytometry.
  • 1C is a view showing the results of confirming the immune phenotype of vascular endothelial cells (HUVEC) according to an embodiment of the present invention by flow cytometry.
  • VEC vascular endothelial cells
  • 1D is a view showing the results of confirming the bone differentiation ability and adipocyte differentiation ability of tooth-derived stem cells according to an embodiment of the present invention.
  • FIG. 2A is a view showing a result of confirming the effect of treating inflammation and muscle damage of tooth-derived stem cells and vascular endothelial cells by H&E staining in a peripheral arterial disease model according to an embodiment of the present invention.
  • FIG. 2B is a view showing a result of confirming the effect of inhibiting fibrosis induction of tooth-derived stem cells and vascular endothelial cells in a peripheral arterial disease model according to an embodiment of the present invention by Masson's trichrome (MT) staining.
  • MT Masson's trichrome
  • FIG. 3 is a view showing the results of confirming the blood vessel formation ability of tooth-derived stem cells and vascular endothelial cells with a Matrigel plug in a peripheral arterial disease model according to an embodiment of the present invention.
  • FIG. 4A is a schematic diagram showing an overall experimental method for confirming the therapeutic effect of tooth-derived stem cells and vascular endothelial cells for peripheral arterial disease according to an embodiment of the present invention
  • FIG. 4B is a blood flow measurement to confirm the therapeutic effect.
  • FIG. 4C is a diagram showing the result of confirming the degree of ischemia injury.
  • composition comprising tooth-derived stem cells and vascular endothelial cells of the present invention as active ingredients inhibits inflammatory reactions and muscle damage in a peripheral arterial disease model, inhibits the induction of fibrosis, as well as promotes the ability to form blood vessels, thereby creating new blood vessels. Since it can be produced, it is expected that it can be effectively used in the treatment of peripheral arterial diseases caused by various causes.
  • stem cell refers to a concept in a broad sense that collectively refers to undifferentiated cells having the ability to differentiate into various types of body tissue cells, that is, stemness.
  • Stem cells refer to stem cells derived from pulp, periodontal ligaments, roots, dental pouches, root papillae, and gums.
  • dimension refers to a soft tissue-like tissue located in the center of the tooth, and the dimension is surrounded by dentin and includes nerve fibers, blood vessels, and lymphatic vessels.
  • Pulp-derived stem cells refer to stem cells that exist in pulp, and pulp is a tissue from which the neural plate differentiates into a neural crest and originates from it.
  • pulp-derived stem cells are a cell source for the development of cell therapy products for regenerative medicine because pulp is easily accessible and has a high ratio between stem cells and collected tissue volumes. Very useful.
  • the pulp-derived stem cells may be derived from pulp of a human tooth.
  • the teeth are not particularly limited, but teeth or wisdom teeth are preferred. Tooth extraction is a process that must be performed, and wisdom teeth extraction is also very common, and since both teeth are mostly discarded after extraction, it has an advantage in that a separate procedure is not required for collecting tooth stem cells.
  • the pulp-derived stem cells may have the characteristics of mesenchymal stem cells.
  • the pulp stem cells may be those in which the markers are expressed when measuring the expression of markers known to exhibit mesenchymal stem cell characteristics through an analysis method such as FACS, real-time PCR, and immunofluorescence staining.
  • the pulp-derived stem cells may express one or more genes selected from the group consisting of CD29, CD44, CD73, CD90, and CD105, preferably CD29, CD44, CD73, CD90, and CD105 genes It may be to express all of.
  • the pulp-derived stem cells may not express one or more types of hematopoietic stem cell markers selected from the group consisting of CD14, CD34, CD45, CD117, and HLA-DR.
  • the pulp-derived stem cells may not express CD31, which is a vascular endothelial cell marker.
  • peripheral artery disease refers to all vascular diseases induced by inflammation, thrombosis, hyperlipidemia, diabetes, etc. in blood vessels excluding the central artery, preferably severe limb ischemia ( critical limb ischemia), pulmonary thromboangiitis (thromboangiitis obliterans), obliterans atherosclerosis (arteriosclerosis obliterans), polyarteritis nodosa, etc.
  • prevention refers to any action that suppresses or delays the onset of peripheral arterial disease by administration of the composition according to the present invention.
  • treatment refers to any action in which symptoms of peripheral arterial disease are improved or advantageously changed by administration of the composition according to the present invention.
  • “individual” refers to a subject to which the composition of the present invention can be administered, and for example, human or non-human primates, mice, dogs, cats, horses, and cattle It can mean a mammal, but the subject is not limited.
  • the term "pharmaceutical composition” may be characterized in that it is in the form of capsules, tablets, granules, injections, ointments, powders or beverages, and the pharmaceutical composition is intended for humans.
  • the pharmaceutical composition of the present invention may contain a pharmaceutically acceptable carrier.
  • Pharmaceutically acceptable carriers can be used as binders, lubricants, disintegrants, excipients, solubilizers, dispersants, stabilizers, suspending agents, coloring agents, flavoring agents, etc. for oral administration, and buffers, preservatives, painlessness, etc. for injections.
  • Agents, solubilizers, isotonic agents, stabilizers, and the like can be mixed and used, and in the case of topical administration, a base agent, excipient, lubricant, preservative, etc. can be used.
  • the formulation of the pharmaceutical composition of the present invention may be prepared in various ways by mixing with a pharmaceutically acceptable carrier as described above.
  • a pharmaceutically acceptable carrier as described above.
  • for oral administration it can be prepared in the form of tablets, troches, capsules, elixir, suspension, syrup, wafers, etc.In the case of injections, it can be prepared in the form of unit dosage ampoules or multiple dosage forms. have.
  • dragees, gels, pills, powders, granules, suppositories, external preparations, solutions, suspensions, sustained-release preparations, and slurries may be formulated and used.
  • suitable carriers, excipients and diluents for formulation include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, malditol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, and the like may be used.
  • fillers, anti-aggregating agents, lubricants, wetting agents, flavoring agents, emulsifying agents, preservatives, and the like may additionally
  • the route of administration of the pharmaceutical composition according to the present invention is not limited thereto, but oral or parenteral administration is preferable, for example, oral, intravenous, intramuscular, intra-articular, intrasynovial, intraarterial, intramedullary, It includes intrathecal, intracardiac, transdermal, intradermal, subcutaneous, intraperitoneal, intranasal, intestinal, local, sublingual, rectal, intrasternal, intralesional, intracranial, and the like.
  • the dosage of the pharmaceutical composition of the present invention can be varied including the activity of the specific compound used, age, body weight, general health, sex, formula, administration time, route of administration, excretion rate, drug combination and the severity of the specific disease to be prevented or treated. It may vary according to factors, and varies depending on the patient's condition, weight, degree of disease, drug type, route and duration of administration, but may be appropriately selected by those skilled in the art, and from 0.0001 to 500 mg/kg per day or from 0.001 to It can be administered at 500 mg/kg. Administration may be administered once a day, or may be divided several times. The above dosage does not in any way limit the scope of the present invention.
  • the term "cellular therapeutic agent” refers to a drug (US FDA regulation) used for treatment, diagnosis, and prevention with cells and tissues manufactured through isolation, culture and special manipulation from humans, In order to restore the function of cells or tissues, these cells are used to treat, diagnose and prevent diseases through a series of actions such as proliferating and screening living autologous, allogeneic, or xenogeneic cells in vitro, or changing the biological characteristics of cells in other ways. It means a drug used for the purpose of.
  • the administration route of the cell therapy composition of the present invention may be administered through any general route as long as it can reach the target tissue.
  • Parenteral administration for example, intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, or intradermal administration, but is not limited thereto.
  • composition may be formulated in a suitable form with a pharmaceutical carrier generally used for cell therapy.
  • “Pharmacologically acceptable” refers to a composition that is physiologically acceptable and, when administered to a human, does not usually cause allergic reactions or similar reactions such as gastrointestinal disorders and dizziness.
  • Pharmaceutically acceptable carriers include, for example, carriers for parenteral administration such as water, suitable oils, saline, aqueous glucose and glycol, and may further include stabilizers and preservatives. Suitable stabilizers include antioxidants such as sodium hydrogen sulfite, sodium sulfite or ascorbic acid. Suitable preservatives are benzalkonium chloride, methyl- or propyl-paraben and chlorobutanol.
  • Other pharmaceutically acceptable carriers may be referred to as those described in the following literature (Remington's Pharmaceutical Sciences, 19th ed., Mack Publishing Company, Easton, PA, 1995).
  • composition may be administered by any device capable of moving a cell therapeutic agent to a target cell.
  • the cell therapy composition of the present invention may contain a therapeutically effective amount of cell therapy for the treatment of a disease.
  • “Therapeutically effective amount” means the amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal or human, as considered by a researcher, veterinarian, physician or other clinician. , which includes an amount that induces relief of symptoms of the disease or disorder being treated.
  • the optimal cell therapy content can be easily determined by those skilled in the art, and the type of disease, severity of the disease, the content of other ingredients contained in the composition, the type of formulation, and the age, weight, general health status, sex and diet of the patient. , Administration time, administration route and secretion rate of the composition, treatment period, it may be adjusted according to various factors including drugs used simultaneously. It is important to include an amount capable of obtaining the maximum effect in a minimum amount without side effects in consideration of all of the above factors.
  • the daily dose of the stem cells of the present invention is 1.0 ⁇ 10 4 to 1.0 ⁇ 10 11 cells/kg body weight, preferably 1.0 ⁇ 10 5 to 1.0 ⁇ 10 9 cells/kg body weight, divided once or several times. Can be administered.
  • the actual dosage of the active ingredient should be determined in the light of various related factors such as the disease to be treated, the severity of the disease, the route of administration, the weight, age, and sex of the patient. It is not intended to limit the scope of the present invention to any aspect.
  • the composition comprising the cell therapeutic agent of the present invention as an active ingredient is rectal, intravenous (intravenous therapy, iv), intraarterial, intraperitoneal, intramuscular, intrasternal, transdermal, topical, intraocular Alternatively, it can be administered in a conventional manner via an intradermal route.
  • the present invention provides a therapeutic method comprising administering to a mammal a therapeutically effective amount of the cell therapy composition of the present invention.
  • mammal refers to a mammal that is the object of treatment, observation or experiment, and preferably refers to a human.
  • tooth-derived stem cells had typical morphological characteristics of mesenchymal stem cells.
  • the tooth-derived stem cells of the present invention express mesenchymal stem cell markers CD29, CD44, CD73, CD90, and CD105, but hematopoietic stem cell markers CD14, CD34, CD45, CD117, HLA It was confirmed that -DR and CD31, a vascular endothelial cell marker, were not expressed.
  • human umbilical vein endothelial cells were purchased from Promocell and used as vascular endothelial cells, and vascular endothelial cells were cultured using endothelial cell growth medium (Promocell) added with 1% penicillin/streptomycin. I did.
  • endothelial cell growth medium Promocell
  • flow cytometric analysis was performed in the same manner as for tooth-derived stem cells, and the results are shown in FIG. 1C.
  • CD29 and CD105 were highly expressed, and the hematopoietic stem cell markers were not expressed as in the tooth-derived stem cells of the present invention.
  • the differentiation ability of the tooth-derived stem cells obtained in the same manner as in Example 1.1 was confirmed.
  • the tooth-derived stem cells in culture reach 80 to 90% confluence, they are replaced with a medium for inducing bone differentiation or a medium for inducing adipocyte differentiation, and then replaced with a new medium for inducing differentiation every 3 days, Incubated for 3 weeks. After 3 weeks, the cells were washed twice with a phosphate buffer solution, and bone differentiation was confirmed by staining with Alzarin solution, and adipocyte differentiation was confirmed by staining with Oil red O solution. After staining, washing was performed once with a phosphate buffer solution, and washed once again with third distilled water to remove all dyeing reagents, and then the stained cells were dried and observed using an optical microscope. The results are shown in FIG. 1D.
  • tooth-derived stem cells were normally differentiated into osteogenic cells and adipogenic cells.
  • the tooth-derived stem cells obtained by the method of Example 1.1 express a marker of mesenchymal stem cells and are capable of differentiating into adipocytes and bone cells.
  • mice were anesthetized by intraperitoneally administering a zoletyl anesthetic. Then, the skin of the hind limb of the anesthetized mouse was excised using a surgical knife, the muscle was removed to expose the femoral artery, and the middle and end of the femoral artery were strongly tied, and the blood vessels between them were removed, and severe limb ischemia. Animal models were prepared.
  • tooth-derived stem cells and vascular endothelial cells exhibits a therapeutic effect on inflammation, muscle damage, and fibrosis, which are symptoms of peripheral arterial disease
  • 1 ) HBSS administration group 2) tooth-derived stem cells alone, 3) umbilical vein endothelial cells alone, 4) tooth-derived stem cells and umbilical vein endothelial cells, four groups, respectively.
  • cells were prepared at a concentration of 1 X 10 6 cells/80 ⁇ L HBSS, put in a syringe, and injected into three muscles of the area in which peripheral arterial disease was induced to perform cell transplantation. Tooth-derived stem cells and umbilical vein endothelial cells were mixed in a ratio of 1:1.
  • the mouse 14 days after transplantation, the mouse was anesthetized using CO 2 , and a paraffin block was prepared after obtaining the tissue at the site where the cells were transplanted. Then, the prepared paraffin block was cut to a thickness of 5 ⁇ m and then subjected to a diparaffin process, followed by Masson's trichrome (MT) and H&E staining. And observed using a microscope. The results are shown in FIG. 2A for H&E staining results and in FIG. 2B for MT staining results.
  • MT Masson's trichrome
  • FIG. 2A it was confirmed that in the negative control group administered with only HBSS, muscle damage was increased due to the induction of peripheral arterial disease, so that the normal muscle shape was not maintained, and the severity of muscle degeneration was very high. In addition, it was confirmed that infiltration of leukocytes was induced, thereby increasing the inflammatory response at the site where peripheral arterial disease was induced. On the other hand, in the experimental group to which tooth-derived stem cells were administered, it was confirmed that muscle damage and infiltration of leukocytes were also partially reduced.
  • tooth-derived stem cells and vascular endothelial cells promotes blood vessel formation in the peripheral arterial disease site
  • 1) Matrigel alone, 2) tooth Derived stem cells alone, 3) umbilical vein endothelial cells alone, and 4) tooth-derived stem cells and umbilical vein endothelial cells, respectively were administered in four groups.
  • cells were prepared at a concentration of 2 ⁇ 10 6 cells/200 ⁇ L Matrigel, placed in a 25G syringe, and injected subcutaneously in the area in which peripheral arterial disease was induced to perform cell transplantation. Tooth-derived stem cells and umbilical vein endothelial cells were mixed in a ratio of 1:1.
  • the mouse was anesthetized using CO 2 , and the implanted Matrigel was separated, and then a paraffin block was prepared. And the prepared paraffin block was cut to a thickness of 4 ⁇ m, subjected to a diparaffin process, and H&E staining was performed. And observed using a microscope. The results are shown in FIG. 3.
  • the degree of capillary formation was low in the group administered with Matrigel alone, vascular endothelial cells alone, and tooth-derived stem cells alone, but the formation of capillaries in the combined administration of tooth-derived stem cells and umbilical vein endothelial cells. It was confirmed that the red blood cells increased significantly due to the infiltration of red blood cells.
  • the tooth-derived stem cells and vascular endothelial cells are administered in combination, the inflammatory response due to peripheral arterial disease is suppressed, muscle damage is prevented, fibrosis is inhibited, and the blood vessel formation ability is increased.
  • the treatment efficiency can be significantly increased because various conditions of peripheral arterial disease can be simultaneously treated differently from the existing treatment methods that alleviate primary symptoms simply by expanding blood vessels.
  • composition comprising tooth-derived stem cells and vascular endothelial cells of the present invention as active ingredients prevents inflammatory reactions and muscle damage in a peripheral arterial disease model, inhibits fibrosis, and increases blood vessel formation ability. It can be effectively used for the treatment of various peripheral arterial diseases caused by various causes such as sclerosis, thromboembolism, inflammatory mechanisms, etc., and is different from existing treatment methods that alleviate primary symptoms by simply expanding blood vessels. It is expected that the success rate of treatment can be remarkably increased because it can treat various conditions of the disease at the same time.

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Abstract

La présente invention concerne une composition pour la prévention ou le traitement d'une maladie artérielle périphérique comprenant des cellules souches dérivées de dents et des cellules endothéliales vasculaires, et il a été confirmé que, suite à une transplantation cellulaire des cellules souches dérivées de dents et des cellules endothéliales vasculaires selon la présente invention, il se produit des effets de suppression d'une réponse inflammatoire, de prévention de lésions musculaires, d'inhibition de l'induction de la fibrose, et en même temps, d'augmentation de la capacité à former des vaisseaux sanguins, favorisant ainsi l'angiogenèse.
PCT/KR2020/008135 2019-06-24 2020-06-24 Composition pour le traitement d'une maladie artérielle périphérique WO2020262916A1 (fr)

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JP2014168714A (ja) * 2008-03-12 2014-09-18 Japan Health Sciences Foundation 根管充填材
KR20150121588A (ko) * 2014-04-21 2015-10-29 한국생명공학연구원 Oct4 및 Sox2를 이용한 인간 치수강세포의 리프로그래밍 방법 및 이의 용도
US20180126039A1 (en) * 2015-05-08 2018-05-10 Université Catholique de Louvain Compositions comprising mesenchymal stem cells and uses thereof

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006238875A (ja) * 2005-02-04 2006-09-14 National Institute Of Advanced Industrial & Technology ヒト歯乳頭からの幹細胞及びその利用方法
JP2014168714A (ja) * 2008-03-12 2014-09-18 Japan Health Sciences Foundation 根管充填材
KR20140054206A (ko) * 2011-08-10 2014-05-08 디퍼이 신테스 프로덕츠, 엘엘씨 제대 조직―유래 세포를 사용한 말초 혈관 질환의 치료
KR20150121588A (ko) * 2014-04-21 2015-10-29 한국생명공학연구원 Oct4 및 Sox2를 이용한 인간 치수강세포의 리프로그래밍 방법 및 이의 용도
US20180126039A1 (en) * 2015-05-08 2018-05-10 Université Catholique de Louvain Compositions comprising mesenchymal stem cells and uses thereof

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