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WO2020036418A1 - Procédé d'amélioration de fonction et de production en grande quantité de cellules de follicules pileux dans un milieu conditionné de cellules dérivées du placenta - Google Patents

Procédé d'amélioration de fonction et de production en grande quantité de cellules de follicules pileux dans un milieu conditionné de cellules dérivées du placenta Download PDF

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Publication number
WO2020036418A1
WO2020036418A1 PCT/KR2019/010314 KR2019010314W WO2020036418A1 WO 2020036418 A1 WO2020036418 A1 WO 2020036418A1 KR 2019010314 W KR2019010314 W KR 2019010314W WO 2020036418 A1 WO2020036418 A1 WO 2020036418A1
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Prior art keywords
placental
hair follicle
cells
derived
conditioned medium
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PCT/KR2019/010314
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English (en)
Korean (ko)
Inventor
김병수
이승진
김지혜
Original Assignee
고려대학교 산학협력단
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Publication of WO2020036418A1 publication Critical patent/WO2020036418A1/fr

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/0603Embryonic cells ; Embryoid bodies
    • C12N5/0605Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/36Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/98Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/98Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
    • A61K8/981Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of mammals or bird
    • A61K8/985Skin or skin outgrowth, e.g. hair, nails
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/14Drugs for dermatological disorders for baldness or alopecia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00Preparations for affecting hair growth
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/0625Epidermal cells, skin cells; Cells of the oral mucosa
    • C12N5/0627Hair cells
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20Cytokines; Chemokines
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2506/00Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
    • C12N2506/02Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from embryonic cells
    • C12N2506/025Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from embryonic cells from extra-embryonic cells, e.g. trophoblast, placenta

Definitions

  • the present invention relates to a placental-derived cell conditioned medium composition for the production of hair follicle cells containing cytokines of human placenta-derived cells and a method for enhancing the function and mass production of hair follicle cells using the same.
  • High-purity, high-efficiency in vitro culture of stem cells or progenitor cells as a source is essential for the production of clinically applicable cell therapies. The chances are high.
  • omnipotent stem cells can be used to culture omnipotent stem cells, and proliferation and differentiation are possible by the mechanism of CXCR2, a chemokine receptor.
  • the present inventors sought to develop placental derived cell conditioned media applicable to hair follicle culture and production by providing a human placental mimic environment.
  • the present invention was found to be capable of culturing hair follicle cells with high purity and high efficiency as compared with the case where no placental-derived cell conditioned medium was used.
  • An object of the present invention is to provide a placental-derived cell conditioned medium composition for hair follicle cell production and a method for producing hair follicle cells using the same.
  • Another object of the present invention is to provide a placental-derived cell conditioned medium composition for hair follicle cell production or a composition for preventing or treating hair loss comprising the hair follicle cells produced in the medium composition as an active ingredient.
  • a placental-derived cell conditioned medium composition for hair follicle cell production containing cytokines of human placental-derived cells.
  • the human placental-derived cells may be placental-derived fibroblast-like cells separated and cultured in human chorionic valve.
  • 1 selected from Angiogenin, BDNF, IGFBP-2 / 4, IL-6, MCP-1, GRO, GRO-a, IGFBP-6, IL-8, Osteoprotegerin, TIM-1 / 2 and uPAR Or more human hair follicle culture active ingredients.
  • a pharmaceutical composition for preventing or treating hair loss comprising the placental-derived cell conditioned medium composition according to an embodiment of the present invention as an active ingredient.
  • a cosmetic composition for preventing or improving hair loss comprising the placental-derived cell conditioning medium composition according to an embodiment of the present invention as an active ingredient.
  • the step of exposing human placenta-derived cells to the cell growth medium to which the culture medium is added to prepare a placental-derived cell conditioning medium containing cytokines; And culturing the hair follicle cells in the placental-derived cell conditioned medium; Including a hair follicle production method is provided.
  • the human placental-derived cells may be placental-derived fibroblast-like cells separated and cultured in human chorionic valve.
  • the placental-derived cell conditioning medium is Angiogenin, BDNF, IGFBP-2 / 4, IL-6, MCP-1, GRO, GRO-a, IGFBP-6, IL-8, Osteoprotegerin, TIM-1 / And one or more human hair follicle culture active ingredients selected from 2 and uPAR.
  • the culture may be DMEM / F-12.
  • hair follicle cells cultured in placental-derived cell conditioned medium for hair follicle production according to an embodiment of the present invention is provided.
  • the media composition of the present invention enables the production of high quality hair follicle cells by enhancing the functions of the hair follicle cells themselves, such as morphogenesis and maintenance of hair follicle cells, and regeneration ability.
  • the placental-derived cell conditioned medium composition of the present invention uses human-derived cell components as a raw material instead of the growth factor used for conventional hair follicle cell culture, and requires double coating or additional supplementation. Since it can reduce the cost of developing cell therapy products, it is possible to mass-produce hair follicle cells.
  • Figure 1 shows a comparison of cytokines contained in the general medium and placental-derived cell conditioned medium composition.
  • Figure 2 is a morphological comparison of the hair follicle cells cultured in the existing follicle cell growth medium and placental-derived cell conditioning medium composition of the present invention.
  • Figure 3 is confirmed by alkaline phosphatase staining whether the hair follicle cells cultured in the existing hair follicle growth medium and placental-derived cell conditioned medium composition of the present invention to maintain the characteristics of the hair follicle cells.
  • Figure 4 is a graph comparing the ratio of cells positive for alkaline phosphate (ALP) staining of hair follicle cells cultured in the existing follicle cell growth medium and placental-derived cell conditioned medium composition of the present invention.
  • ALP alkaline phosphate
  • Figure 6 shows the expression of the hair follicle-specific transcription factors ALPL and LEF1 by measuring the real-time polymerase chain reaction (Quantitative real-time PCR Analysis)
  • Figure 7 compares the hair growth effect of the placental-derived cell conditioned medium composition and the general medium of the present invention.
  • placental refers to the placenta that is separated after birth from the mother's mother.
  • the placenta can be separated and quickly stored in sterile containers and ice.
  • prevention refers to any action that inhibits or delays hair loss by administration of the composition of the present invention
  • treatment means any action that improves or advantageously changes the symptoms caused by hair loss by the composition of the present invention. Means.
  • conditioned media refers to a medium whose function has been altered by containing active ingredients produced by the cell or factors conducive to the maintenance and survival of the cell.
  • a placental-derived cell conditioned medium composition for hair follicle cell production containing cytokines of human placental-derived cells.
  • the placental-derived cell conditioned medium of the present invention may be prepared by exposing the placental-derived cells to a cell growth medium to which the culture solution is added and extracting human hair follicle culture active ingredients such as cytokines.
  • the culture medium used for the preparation of the placental-derived cell conditioned medium composition may be a conventional culture medium in which fetal calf serum and the like are excluded, and preferably DMEM / F-12 containing serum replacement, a sulfate agent, and an antibiotic.
  • DMEM / F-12 supplemented with 20% Knockout Serum Replacer (GIBCO), 0.1 mM ⁇ mercaptoethanol, and 1% penicillin-streptomycin (Sigma) may be used.
  • the human placental-derived cells included in the placental-derived cell conditioned medium composition of the present invention may be placental-derived fibroblast-like cells separated and cultured in a human chorionic plate.
  • the placental fibroblast-like cells can be obtained from the following process:
  • the placental-derived cell conditioned medium may comprise a human hair follicle culture active ingredient.
  • human hair follicle culture active ingredients are Angiogenin, BDNF, IGFBP-2 / 4, IL-6, MCP-1, GRO, GRO-a, IGFBP-6, IL-8, Osteoprotegerin, TIM-1 / 2 and It may be one or more selected from uPAR. Since the conditioned medium of the present invention contains such follicle cell culture active ingredients, the production of follicle cells can be promoted more efficiently.
  • the placental-derived cell conditioned medium composition of the present invention may further comprise a knockout serum replacement (Knockout Serum Replacement) to increase the culture efficiency.
  • Knockout Serum Replacement knockout Serum Replacement
  • the placental-derived cell conditioning medium of the present invention is composed of only human-derived products, it is possible to produce hair follicle cells with high purity and high efficiency, and to prevent contamination by heterologous proteins or cells, and thus, in the cell conditioning medium.
  • the use of cultured hair follicle cells can improve the stability and efficacy in the clinic.
  • hair loss preventing or treating pharmaceutical composition comprising follicle cells cultured in placental-derived cell conditioned medium or placental-derived cell conditioned medium according to an embodiment of the present invention as an active ingredient, Is provided.
  • the pharmaceutical composition may be prepared by a method known in the pharmaceutical field to be used as a medicament, and may be used in combination with a pharmaceutically acceptable carrier, excipient, diluent, stabilizer, preservative, and the like.
  • the diluent may be a non-aqueous solvent such as propylene glycol, polyethylene glycol, vegetable oils such as olive oil and peanut oil, or brine (preferably 0.8% saline), water containing a buffer medium (preferably 0.05M phosphate buffer)
  • aqueous solvent such as these, etc. are mentioned, but it is not limited to this.
  • excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, anhydrous skim milk, glycerol, propylene, glycol, water , Ethanol and the like, but is not limited thereto.
  • the stabilizer may include carbohydrates such as sorbitol, mannitol, starch, sucrose, dextran, glutamate, and glucose, and proteins such as animal, vegetable or microbial proteins such as milk powder, serum albumin and casein, but are not limited thereto. no.
  • the preservative may include thimerosal, merthiolate, gentamicin, neomycin, nistatin, amphotericin B, tetracycline, penicillin, streptomycin, polymyxin B, and the like, but is not limited thereto.
  • the method of administration of the pharmaceutical composition of the present invention is not particularly limited, but may be administered orally, or preferably, applied to a hair loss site or to a site where the progress of hair loss is foreseen.
  • the method of administration is not particularly limited, so it is possible to inject directly into the site where hair loss or hair loss is expected in the form of injection or by injection into an artery or vein.
  • the pharmaceutical composition of the present invention may be formulated as a "transdermal dosage form” and used for the prevention or treatment of hair loss.
  • a "transdermal formulation” is a formulation that is effective by administering a drug through the skin, and is formulated in the form of a drug applied to the skin, a drug applied to the skin, and the like.
  • skin permeation of the active ingredient is achieved through the intracellular, intercellular or adnexal organs such as pores and hair pores by simple diffusion according to the concentration gradient.
  • This has the disadvantage that it is not easy to pass through the undamaged skin, but it is easy to use such as the efficiency of the drug, the control of the administration rate, and the possibility of direct application to the affected area.
  • There are advantages such as minimizing and reducing the burden on the liver.
  • In order to facilitate the skin penetration of the active ingredient may be formulated additionally comprising a skin administration accelerator.
  • transdermal formulation may be used without limitation as long as the formulation can directly administer the active ingredient to the surface of the diseased part of the skin.
  • ointments creams, gels, lotions, liquids, emulsions, suspensions, warnings (sticks), pasta, linen, pape, tape, aerosol or external acid, etc. It can be prepared and used.
  • hair follicle cells cultured in placental-derived cell or placental-derived cell conditioned medium comprising a medium as an active ingredient, hair loss prevention or cosmetic composition for improvement This is provided.
  • the cosmetic composition of the present invention may include without limitation the conventionally acceptable ingredients in addition to the active ingredient, and includes conventional auxiliaries such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavors, and carriers. can do.
  • conventional auxiliaries such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavors, and carriers. can do.
  • the cosmetic composition may be used in a shampoo, rinse, treatment or scalp care agent.
  • the step of exposing human placenta-derived cells to the cell growth medium to which the culture medium is added to prepare a placental-derived cell conditioned medium containing cytokines; And culturing the hair follicle cells in the placental-derived cell conditioned medium; Including a hair follicle production method is provided.
  • the components and preparation method of placental-derived cell conditioned medium for hair follicle production used in the hair follicle production method are as described above.
  • the hair follicle production method of the present invention is not limited to the production of human hair follicle cells, can be utilized in the production of hair follicle cells of various animals such as dogs, cows, sheep, pigs.
  • hair follicle cells cultured in a placental-derived cell conditioned medium composition for hair follicle production is provided.
  • the hair follicle cells maintain the morphological characteristics of the hair follicle cells well, and have a higher degree of specific factor expression and hair induction capacity than the hair follicle cells cultured in the existing hair follicle cell production medium.
  • the hair follicle cells cultured in the conditioned medium composition of the present invention can be used as a cell therapeutic agent for the prevention or treatment of hair loss per se, or as a pharmaceutical composition or cosmetic composition comprising the same as an active ingredient.
  • Placental cells were obtained from placental tissue isolated by surgical operation with a caesarean section after written consent from a healthy pregnant woman who had a therapeutic miscarriage at 7 weeks of pregnancy. Isolate the cells from the chorionic villus of the placenta and isolate the placental cells with 20% fetal bovine serum (FBS), 100 U / ml penicillin and 100 g / ml streptomycin. Placental cells were obtained by culturing for one week in a flask containing DMEM (Dulbecco's modified Eagle's medium) and coated with 0.1% gelatin.
  • FBS fetal bovine serum
  • Placental cells were obtained by culturing for one week in a flask containing DMEM (Dulbecco's modified Eagle's medium) and coated with 0.1% gelatin.
  • Placental-derived cell conditions containing cytokines by 24 hour exposure of placental cells in media consisting of DMEM / F-12, 20% Knockout Serum replacement, 0.1 mM ⁇ -mercaptoethanol, and 1% penicillin streptomycin from GIBCO Media composition was prepared.
  • Placenta-derived cell conditioned medium composition was used as a control medium (DMEM / F12) as a control, and the placental-derived cell conditioned medium composition was prepared using Ray Biotech's Human cytokine antibody array kit to search for active hair follicle culture.
  • the cytokines contained were analyzed and shown in FIG.
  • an essential ingredient necessary for culturing hair follicle cells was determined using a dot signal: Angiogenin, BDNF, IGFBP-2 / 4, IL-6, MCP-1, GRO, GRO-a, IGFBP-6 , IL-8, Osteoprotegerin, TIM-1 / 2, uPAR.
  • the hair follicle cells cultured in the placental-derived cell conditioned medium composition prepared in Example 1 is grown while maintaining the morphological characteristics of the hair follicle cells better than that cultured in the existing follicle cell growth medium You can check it.
  • the hair follicle cells cultured in the conditioned medium composition of the present invention was confirmed that the expression level of alkaline phosphatase is three times or more compared to the control cultured in the conventional growth medium.
  • the hair follicle cells cultured in the conditioned medium composition of the present invention can be confirmed that the morphogenesis and regeneration function is enhanced compared to the hair follicle cells cultured in the existing growth medium.
  • hair follicle specific factors CD29 and CD90 were measured by flow cytometry.
  • flow cytometry hair follicle cells were cultured and harvested in a placental-derived conditioned medium composition for 48 hours, 1X10 5 cells were dispensed in FACS tube, and CD29, CD90 (BioLegend) primary antibody was left at 4 ° C for 30 minutes. Measurement was performed by flow cytometry (BD FACSCanto II).
  • RNA is isolated from hair follicle cells using a kit (Qiagen RNeasy kit, Qiagen Hilden, Germany), and cDNA using 2 ug of RNA, oligo (dT) and reverse transcriptase (Superscript II reverse transcriptase, Gibco). Synthesized. Each synthesized cDNA was put into the primer and master mix (iQ SYBR Green qPCR Master Mix) for ALPL and LEF1 detection and analyzed using a device (Bio-Rad iCycler iQ system, Bio-Rad Laboratories, USA). Assay values were normalized using the GAPDH gene.
  • the hair follicle cells cultured in the placental-derived cell conditioned medium composition of the present invention express CD29 and CD90, which are characteristic of hair follicle cells, and as shown in FIG. 6, hair follicle-specific transcription factors compared to the control group. It can be seen that it expresses more of ALPL and LEF1.
  • Placenta-derived hairs prepared with the composition of placenta-derived cell conditioned medium of the present invention prepared in Example 1 and DMEM / F-12, 20% Knockout Serum replacement, 0.1 mM ⁇ -mercaptoethanol, and 1% penicillin streptomycin One rat was applied once a day for 5 days and then the hair growth effect was compared.
  • the conditioned medium composition of the present invention is effective for the production of hair follicle cells.

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Abstract

La présente invention concerne un milieu conditionné de cellules dérivées du placenta pour la production de cellules de follicules pileux, un procédé de production de cellules de follicules pileux à l'aide de celui-ci, et une composition pharmaceutique permettant de prévenir ou de traiter la perte des cheveux, contenant, en tant que principe actif, le milieu conditionné de cellules dérivées du placenta ou les cellules de follicules pileux.
PCT/KR2019/010314 2018-08-17 2019-08-13 Procédé d'amélioration de fonction et de production en grande quantité de cellules de follicules pileux dans un milieu conditionné de cellules dérivées du placenta WO2020036418A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020180096160A KR20200020438A (ko) 2018-08-17 2018-08-17 태반유래 세포 조건화 배지에서의 모낭세포 기능강화 및 대량생산 방법
KR10-2018-0096160 2018-08-17

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WO2020036418A1 true WO2020036418A1 (fr) 2020-02-20

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Families Citing this family (1)

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KR102151501B1 (ko) * 2020-05-26 2020-09-03 박성은 모발 또는 두피 건강 개선용 조성물

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101199837A (zh) * 2007-11-30 2008-06-18 何荫良 一种人源性细胞因子生发制剂及其制备方法
KR20120118407A (ko) * 2011-04-18 2012-10-26 고려대학교 산학협력단 태반유래세포에 조건화된 배양 배지, 및 이를 이용한 무동물 및 무지지세포 줄기세포 배양 방법
US20130171112A1 (en) * 2007-07-24 2013-07-04 Stemnion, Inc. Methods for promoting hair growth
WO2016159721A1 (fr) * 2015-04-03 2016-10-06 (유)스템메디케어 Procédé de production en masse de protéines dans des cellules souches mésenchymateuses
KR20160143837A (ko) * 2014-07-07 2016-12-14 메디포스트(주) 자극된 줄기세포 배양액의 발모 촉진능 및 이의 용도
KR20160145778A (ko) * 2014-07-07 2016-12-20 메디포스트(주) 작은 크기 줄기세포의 발모 촉진능 및 이의 용도

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130171112A1 (en) * 2007-07-24 2013-07-04 Stemnion, Inc. Methods for promoting hair growth
CN101199837A (zh) * 2007-11-30 2008-06-18 何荫良 一种人源性细胞因子生发制剂及其制备方法
KR20120118407A (ko) * 2011-04-18 2012-10-26 고려대학교 산학협력단 태반유래세포에 조건화된 배양 배지, 및 이를 이용한 무동물 및 무지지세포 줄기세포 배양 방법
KR20160143837A (ko) * 2014-07-07 2016-12-14 메디포스트(주) 자극된 줄기세포 배양액의 발모 촉진능 및 이의 용도
KR20160145778A (ko) * 2014-07-07 2016-12-20 메디포스트(주) 작은 크기 줄기세포의 발모 촉진능 및 이의 용도
WO2016159721A1 (fr) * 2015-04-03 2016-10-06 (유)스템메디케어 Procédé de production en masse de protéines dans des cellules souches mésenchymateuses

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