DE202018003814U1 - Antipsoriatic gel for skin application II - Google Patents

Antipsoriatic gel for skin application II Download PDF

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DE202018003814U1
DE202018003814U1 DE202018003814.8U DE202018003814U DE202018003814U1 DE 202018003814 U1 DE202018003814 U1 DE 202018003814U1 DE 202018003814 U DE202018003814 U DE 202018003814U DE 202018003814 U1 DE202018003814 U1 DE 202018003814U1
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • 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
    • 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
    • A61K35/48—Reproductive organs
    • A61K35/50—Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0028—Polypeptides; Proteins; Degradation products thereof
    • A61L26/0033—Collagen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0057—Ingredients of undetermined constitution or reaction products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061—Use of materials characterised by their function or physical properties
    • A61L26/008—Hydrogels or hydrocolloids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • 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
    • C12N5/0663—Bone marrow mesenchymal stem cells (BM-MSC)
    • 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
    • C12N2533/00—Supports or coatings for cell culture, characterised by material
    • C12N2533/50—Proteins
    • C12N2533/54—Collagen; Gelatin

Abstract

Die in vitro Erzeugung von Knochenmark- MSCs in Kollagengel Kulture, das für Hautanwendung bei Psoriasis und ähnliche Läsionen appliziert werden kann.The in vitro production of bone marrow MSCs in collagen gel culture, which can be applied for skin application in psoriasis and similar lesions.

Description

Psoriasis ist eine häufig aufgetretende immunvermittelte, chronisch entzündliche Hauterkrankung, die durch hyperproliferative Keratinozyten und eine starke Infiltration verschiedener Leukozyten, einschließlich T-Zellen, dendritischer Zellen (DC), Makrophagen und Neutrophilen verursacht wird. Unter diesen Leukozyten spielen T-Zellen eine zentrale Rolle bei der Entwicklung der Erkrankung. Insbesondere hyperaktivierte Th1- und Th17-Reaktionen werden häufig im Blut und in der Haut von Psoriasis- Patienten bemerkt und gelten als verantwortlich für psoriatische Dermatitis (1,2).Psoriasis is a common immune-mediated, chronic inflammatory skin disease caused by hyperproliferative keratinocytes and strong infiltration of various leukocytes, including T cells, dendritic cells (DC), macrophages and neutrophils. Among these leukocytes, T cells play a central role in the development of the disease. In particular, hyperactivated Th1 and Th17 responses are commonly recognized in the blood and skin of psoriatic patients and are considered to be responsible for psoriatic dermatitis (1,2).

Positive und negative co-regulatorische Signale regulieren die Aktivität der T-Zellen. Diese Signale werden durch die Interaktion von Co-regulatorischen Rezeptore n (exprimiert auf T-Zellen) und ihren Liganden (auf Antigen-präsentierenden Zellen und nicht- lymphoiden Zellen) geliefert. Zu den positiven Regulatoren (oder Costimulatoren) gehören CD28: CD80 / CD86-, CD40: CD40L- und OX40: OX40L-Paarungsrezeptoren. Die negativen Regulatoren (oder Co-Inhibitoren) umfassen CTLA-4: CD80/ CD86 und PD-1: PD-L1 / PD-L2.Positive and negative co-regulatory signals regulate the activity of T cells. These signals are provided by the interaction of co-regulatory receptors n (expressed on T cells) and their ligands (on antigen-presenting cells and non-lymphoid cells). Positive regulators (or costimulators) include CD28: CD80 / CD86, CD40: CD40L and OX40: OX40L mating receptors. The negative regulators (or co-inhibitors) include CTLA-4: CD80 / CD86 and PD-1: PD-L1 / PD-L2.

Bei Psoriasis- Patienten ist die Expression von Kostimulatoren in hyperaktivierten T-Zellen und anderen Leukozyten, im Vergleich zu gesunden Kontrollen, signifikant erhöht. Die Behandlung von Psoriasis-Patienten oder psoriatischen Hauttransplanten in SCID- Mäusen mit Co-Stimulator- spezifischen Inhibitoren (Antikörper oder Chemikalien) reduziert Akanthose und Lymphozyten- Hautinfiltrate, was darauf hinweist, dass die Stimulatoren eine entscheidende Rolle bei der Entstehung psoriatischer Haut spielen. Obwohl angenommen wird, dass die T-Zellen-Hyperaktivierung auch auf eine fehlregulierte Expression oder einen Mangel in der Funktion von Co-Inhibitoren zurückzuführen ist, ist wenig über ihren Beitrag zur Pathogenese bekannt (3).In psoriatic patients, the expression of costimulants in hyperactivated T cells and other leukocytes is significantly increased compared to healthy controls. Treatment of psoriasis patients or psoriatic skin transplants in SCID mice with co-stimulator-specific inhibitors (antibodies or chemicals) reduces acanthosis and lymphocyte skin infiltrates, suggesting that stimulators play a crucial role in the development of psoriatic skin. Although it is believed that T cell hyperactivation is also due to a misregulated expression or deficiency in the function of co-inhibitors, little is known about its contribution to the pathogenesis (3).

Mesenchymale Stammzellen (MSCs) sind multipotente Stromazellen Zellen, die auch aus adultem Knochenmark und andere Gewebe stammen können. Diese Zellen haben die Fähigkeit in viele Zelllinien zu differenzieren, einschließlich Hautzellen. MSCs können eine wichtige Rolle in der Kontrolle und / oder Vorbeugung der Autoimmunerkrankungen und entzündliche Zustände spielen (4,5).Mesenchymal stem cells (MSCs) are multipotential stromal cells that can also originate from adult bone marrow and other tissues. These cells have the ability to differentiate into many cell lines, including skin cells. MSCs may play an important role in the control and / or prevention of autoimmune diseases and inflammatory conditions (4,5).

Mesenchymale Stammzellen werden vom Immunsystem sehr toleriert, wo sie die Immunität durch die Modulation der T - Zell - Aktivierung und - Proliferation, sowohl durch eine direkte Zell-Zell-Interaktionen oder sekretierte Mediatoren abschwächen können. Diese Fähigkeiten sind unabhängig von der Haupthistokompatibilität (MHC) -Matching und können über Spezies wirken, da MSCs sehr niedrige Expression von MHC I und II zeigen, und die T-Zelle kostimuliere nd Moleküle CD80 und CD86 fehlen.Mesenchymal stem cells are highly tolerated by the immune system, where they can attenuate immunity by modulating T cell activation and proliferation through either direct cell - cell interactions or secreted mediators. These abilities are independent of major histocompatibility (MHC) matching and can function across species, as MSCs show very low expression of MHC I and II, and lack the T cell costimulatory molecules CD80 and CD86.

Deswegen wird die Transplantation von Allo-MSCs für die Attenuierung der Graft- versus- Host- Reaktion verwendet (6). Die MSCs produzieren viele Faktoren, zum Beispiel IL10, transformierender Wachstumsfaktor (TGF), Prostaglandin E2 (PGE2) und vaskulärer β endothelialer Wachstumsfaktor (VEGF) (5,6). IL10 ist eines der wichtigsten entzündungshemmenden Zytokine, das die Expression von Zytokinen im T Helfer- 1-Zellen, sowie die Haupthistokompatibilitätsklasse II Antigene und kostimulatorische Moleküle auf der Oberfläche von Makrophagen runter reguliert. Darüber hinaus antagonisiert IL10 die Aktivität von NF- KB und ist in der Lage, die Produktion von IL8 in dosisabhängiger Weise unterzudrücken (7,8).Therefore, Allo-MSC transplantation is used to attenuate the graft-versus-host response (6). The MSCs produce many factors, for example, IL10, transforming growth factor (TGF), prostaglandin E2 (PGE2), and vascular beta endothelial growth factor (VEGF) (5,6). IL10 is one of the major anti-inflammatory cytokines that regulates the expression of cytokines in T helfer 1 cells, as well as major histocompatibility class II antigens and co-macrophage costimulatory molecules. In addition, IL10 antagonizes the activity of NF-κB and is able to suppress the production of IL8 in a dose-dependent manner (7,8).

Während der Haftfähigkeit der Endothelzellen bei IL1, TNF- alpha, IFN- β und gamma; und Lipopolysaccharid- Stimulation signifikant zunimmt, was die Migration von Leukozyten (Makrophagen und Lymphozyten) zu Entzündungshautläsionen erhöht, hat das von MSCs skretierte TGF β die Fähigkeit, diese Effekte in einer Dosisabhängig zu blockieren (9).During adhesiveness of endothelial cells in IL1, TNF-alpha, IFN-β and gamma; and lipopolysaccharide stimulation increases significantly, which increases the migration of leukocytes (macrophages and lymphocytes) into inflammatory skin lesions, the MSF-secreted TGFβ has the ability to dose-dependently block these effects (9).

PGE2 wirkt auf die Hemmung der Proliferation, Differenzierung und Funktion der Antigen- präsentierten und zytotoxischen Zellen, einschließlich den dendritischen Zellen, Makrophagen und natürliche Killerzellen (NK) (10). Inzwischen hat VEGF neuroprotektive Wirkungen, wobei es das Überleben von Nervenenden verbessern kann (11). Daher könnte die Verwendung von MSCs in den Fällen von Psoriasis und anderen Autoimmun- basierten Hauterkrankungen auf die Abschwächung der aggressiven Immunsystemsreaktionen hinarbeiten, zusammen mit der möglichen regenerativen Erholung der Haut.PGE2 acts to inhibit the proliferation, differentiation, and function of antigen-presenting and cytotoxic cells, including dendritic cells, macrophages, and natural killer (NK) cells (10). Meanwhile, VEGF has neuroprotective effects, whereby it can improve the survival of nerve endings (11). Therefore, the use of MSCs in the cases of psoriasis and other autoimmune skin diseases could work to attenuate the aggressive immune system responses, along with the possible regenerative recovery of the skin.

Das Hauptanliegen dieser therapeutischen Strategie könnte das Risiko der Einbeziehung von MSCs in Krebs Entwicklung sein, was nicht vollständig ausgeschlossen werden kann, ohne die Anwendung von langfristigen klinischen Studien. Aber es scheint beruhigend zu sein, wenn das proliferative Potenzial des menschenlichen nabelschnur- perivaskulären MSCs (HUCPVMSCs) mit dem der Knochenmarken- MSCs (BMMSCs) vergleicht wurde. Beide Zellen zeigten ähnliche Proliferationsraten zum Beginn zu haben, jedoch zwischen den 7. und 14. Tag hatten die HUCPVMSCs signifikantliferationsrate während die BMMSCs auf Kontaktinhibierung gut reagierten und mit der Proliferation aufhörten. HUCPVMSCs haben sich aber weiter vermehrten, was zur Mehrschichtigkeit führte. In ähnlicher Weise zeigten HUCPVMSCs höhere Differenzierungskapazität (12).The main concern of this therapeutic strategy could be the risk of including MSCs in cancer development, which can not be fully ruled out without the use of long-term clinical trials. But it seems reassuring to compare the proliferative potential of human umbilical perivascular MSC (HUCPVMSCs) with that of bone marrow MSCs (BMMSCs). Both cells showed similar rates of proliferation at baseline, however, between days 7 and 14, HUCPVMSCs had significant liferation rates while BMMSCs responded well to contact inhibition and ceased proliferation. HUCPVMSCs have continued to multiply, resulting in multi-layeredness. Similarly, HUCPVMSCs showed higher differentiation capacity (12).

Die Idee der Anwendung von Plazenta- Stammzellen in der Therapie von Psoriasis wrude früher eingeführt ( US875388 3B 2: A method of treating an individual at risk of developing psoriasis, comprising administering to the individual a therapeutically effective amount of placental stem cells, wherein the therapeutically effective amount is an amount sufficient to cause a detectable improve ment in one or more symptoms of said psoriasis; and wherein said placental stem cells are CD34-, CD10+, CD105+, and CD200+). (Verfahren zur Behandlung eines Individuums mit einem Risiko, Psoriasis zu entwickeln, umfassend Verabreichen einer therapeutisch wirksamen Menge von Plazenta-Stammzellen an das Individuum, wobei die therapeutisch wirksame Menge eine Menge ist, die ausreicht, um eine nachweisbare Verbesserung von einem oder mehreren Symptomen der Psoriasis zu bewirken; und wobei die Plazenta-Stammzellen CD34-, CD10 +, CD105 + und CD200 + sind). The idea of using placental stem cells in the treatment of psoriasis was earlier introduced ( US875388 3B 2: A concept for the treatment of psoriasis is provided psoriasis; and said placental stem cells are CD34-, CD10 +, CD105 +, and CD200 +). A method of treating an individual at risk of developing psoriasis comprising administering to the subject a therapeutically effective amount of placental stem cells, wherein the therapeutically effective amount is an amount sufficient to provide a detectable improvement in one or more symptoms of the subject Psoriasis, and wherein the placenta stem cells are CD34, CD10 +, CD105 + and CD200 +).

Die Idee der Anwendung von MSCs in Hemmun g der entzündlichen Status in vivo wurde früher eingeführt ( WO2017062 4 7 5A 1; wobei die MSCs Fettgewebe-abgeleitete mesenchymale Stammzellen sind). Ebenso die Idee der Anwendung vom Kollagengel für Hautanwendung wurde früher eingeführt (das Medikament ist auf dem Markt bekannt).The idea of using MSCs in inhibiting inflammatory status in vivo was earlier WO2017062 4 7 5A 1; where the MSCs are adipose tissue-derived mesenchymal stem cells). Likewise the idea of application of collagen gel for skin application was introduced earlier (the drug is known on the market).

Hier geht es um die in vitro Erzeugung von Knochenmark- MSCs in Kollagengel Kulture, das für Hautanwendung bei Psoriasis und ähnliche Läsionen appliziert werden kann. Das Gel wird mit den Mediatoren geflutet, die von den Zellen sekretiert werden. Mit rechtzeitiger korrekter und wiederholter Anwendung solches Gels auf den psoriatischen Läsionen wird es erwartet, dass eine hochgradige T-Zell-Hemmung und Anti-Autoimmunaktivität erreicht werden. Da die Zellen unter den exponierten Bedingungen nicht viel überleben werden und da es in den psoriatischen Läsionen zunächst keine Krebszellen gibt, sollen die immunsuppressiven Vorteile ohne ungewünschte Neubildung von Neoplasmen erzielt werden.This is about the in vitro production of bone marrow MSCs in collagen gel culture, which can be applied for skin application in psoriasis and similar lesions. The gel is flooded with the mediators that are secreted by the cells. Timely correct and repeated application of such gel to the psoriatic lesions is expected to result in high level T cell inhibition and anti-autoimmune activity. Since the cells will not survive much under the exposed conditions and since there are initially no cancer cells in the psoriatic lesions, the immunosuppressive benefits should be achieved without unwanted neoplasm formation.

Dennoch wird erwartet, dass die Zellen und die von den Zellen sezernierten Mediatoren die Autoimmunreaktion, die die Läsionen erzeugt, wirksamunterdrücken, die Neovaskularisation und die Regeneration der Haut begünstigen, und zusammen mit dem Kollagengel zusätzlich die Heilung der Hautläsionen und die Begrenzung der Restentformung verbessern.Nevertheless, it is expected that the cells and the mediators secreted by the cells will effectively suppress the autoimmune reaction that produces the lesions, promote neovascularization and skin regeneration, and in addition, together with the collagen gel, improve the healing of skin lesions and the limitation of residual demolding.

Technische BemerkungenTechnical remarks

  • • Die Isolierung und / oder Erzeugung der MSCs wird einer der veröffentlichten Techniken folgen.The isolation and / or generation of the MSCs will follow one of the published techniques.
  • • Das medizinische Produkt wird auf eine geeignete Lebensfähigkeit der Zellen sowie auf eine geeignete Zellzahl und Überleben pro Dosierung eingestellt.• The medicinal product is adjusted for proper viability of the cells as well as for a suitable cell count and survival per dosage.
  • • Präklinische und klinische Studien werden durchgeführt, um die Wirksamkeit und Sicherheit der therapeutischen Strategie zu dokumentieren.• Preclinical and clinical studies are conducted to document the efficacy and safety of the therapeutic strategy.
  • • Die in vitro Zellkultur in Kollagengel ist möglich und anwendbar (13).• In vitro cell culture in collagen gel is possible and applicable (13).
  • • Die Verwendung vom Kollagengel ist an sich bekannt und in vielen Ländern zur Verbesserung der Jugendlichkeit und der Restbeanspruchung der Haut zugelassen.• The use of collagen gel is well known and approved in many countries to improve youthfulness and residual stress on the skin.

Quellesource

  1. 1. Rivas Bejarano JJ, Valdecantos WC. Psoriasis as autoinflammatory disease. Dermatol Clin. 2013 Jul;31(3):445- 60 .1. Rivas Bejarano JJ, Valdecantos WC. Psoriasis as autoinflammatory disease. Dermatol Clin. 2013 Jul; 31 (3): 445-60 ,
  2. 2. Lowes MA, Suárez- Fariñas M, Krueger JG. Immunology of psoriasis. AnnuAnnu Rev Immunol. 2014; 32: 227- 55 .Second Lowes MA, Suárez-Fariñas M, Krueger JG. Immunology of psoriasis. AnnuAnnu Rev Immunol. 2014; 32: 227-55 ,
  3. 3. Lauren Y. Cao, Jin-Sung Chung, Takahiro Teshima, Lawrence Feigenbaum, Ponciano D. Cruz, Jr., Heidi T. Jacobe, Benjamin F. Chong, and Kiyoshi Ariizumi. Myeloid- derived Suppressor Cells in Psoriasis are an Expanded Population Exhibiting Diverse T cell- Suppressor Mechanisms. J Invest Dermatol. 2016; 136(9): 1801-1810 .Third Lauren Y. Cao, Jin-Sung Chung, Takahiro Teshima, Lawrence Feigenbaum, Ponciano D. Cruz, Jr., Heidi T. Jacobe, Benjamin F. Chong, and Kiyoshi Ariizumi. Myeloid-derived Suppressor Cells in Psoriasis are Expanded Population Exhibiting Diverse T cell Suppressor Mechanisms. J Invest Dermatol. 2016; 136 (9): 1801-1810 ,
  4. 4. Zeng R, Wang LW, Hu ZB, Guo WT, Wei JS, Lin H, et al. Differentiation of human bone marrow mesenchymal stem cells into neuron- like cells in vitro. Spine (Phila Pa 1976) 2011;36:997- 1005 .4th Zeng R, Wang LW, Hu ZB, Guo WT, Wei JS, Lin H, et al. Differentiation of human bone marrow mesenchymal stem cells into neuron-like cells in vitro. Spine (Phila Pa 1976) 2011; 36: 997-1005 ,
  5. 5. Salgado AJ, Sousa JC, Costa BM, Pires AO, Mateus- Pinheiro A, Teixeira FG, et al. Mesenchymal stem cells secretome as a modulator of the neurogenic niche: basic insights and therapeutic opportunities. Front Cell Neurosci 2015;9:249 .5th Salgado AJ, Sousa JC, Costa BM, Pires AO, Mateus-Pinheiro A, Teixeira FG, et al. Mesenchymal stem cells secretome as a modulator of neurogenic diseases: basic insights and therapeutic opportunities. Front Cell Neurosci 2015; 9: 249 ,
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  8. 8. Mendez- Samperio P, Garcia E, Vázquez A, Palma J. Regulation of Interleukin- 8 by Interleukin-10 and Transforming Growth Factor in β Human Monocytes Infected with Mycobacterium bovis. Clin Diagn Lab Immunol 2002;9:802-70 .8th. Mendez-Samperio P, Garcia E, Vázquez A, Palma J. Regulation of Interleukin-8 by Interleukin-10 and Transforming Growth Factor in β Human Monocytes Infected with Mycobacterium bovis. Clin Diagn Lab Immunol 2002; 9: 802-70 ,
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  10. 10. Agard M, Asakrah S, Morici LA. PGE2 suppres sion of innate immunity during mucosal bacterial infection. Front Cell Infect Microbiol 2013;3:45 .10th Agard M, Asakrah S, Morici LA. PGE2 suppression of innate immunity during mucosal bacterial infection. Front Cell Infect Microbiol 2013; 3: 45 ,
  11. 11. Duffy AM, Bouchier- Hayes DJ, Harmey JH. Vascular Endothelial Growthr (VEGF) and Its Role in Non- Endothelial Cells: Autocrine Signalling by VEGF. In: Madam e Curie Bioscience Databas e (Interne t). Austin (TX): Landes Bioscience; 2000-2013 .11th Duffy AM, Boucher-Hayes DJ, Harmey JH. Vascular Endothelial Growthr (VEGF) and Its Role in Non-Endothelial Cells: Autocrine Signaling by VEGF. In: Madame e Curie Bioscience Databas e (Interne t). Austin (TX): Landes Bioscience; 2000-2013 ,
  12. 12. Baksh D, Yao R, Tuan RS. Comparison of Proliferative and Multilineage Differentiation Potential of Human Mesenchymal Stem Cells Derived from Umbilical Cord and Bone Marrow. Stem Cells 2007;25:1384-92. https://doi.org/10.1634/ stemcells.2006- 0709 .12th Baksh D, Yao R, Tuan RS. Comparison of Proliferative and Multilineage Differentiation Potential of Human Mesenchymal Stem Cells Derived from Umbilical Cord and Bone Marrow. Stem Cells 2007; 25: 1384-92. https://doi.org/10.1634/ stemcells.2006-0709 ,
  13. 13. LIU, Y. and WILLIAMS, D.J. Processing of collagen gels to create in vitro cell growth matrix without damage to the collagen native structure. Proceedings of the Institution of Mechanical Engineers, Part B: Journal of Engineering Manufacture, 2006; 220 (5), pp. 787- 791 .13th LIU, Y. and WILLIAMS, DJ Processing of collagen gels to create in vitro cell growth matrix without damage to the collagen native structure. Proceedings of the Institution of Mechanical Engineers, Part B: Journal of Engineering Manufacture, 2006; 220 (5), pp. 787-791 ,

ZITATE ENTHALTEN IN DER BESCHREIBUNG QUOTES INCLUDE IN THE DESCRIPTION

Diese Liste der vom Anmelder aufgeführten Dokumente wurde automatisiert erzeugt und ist ausschließlich zur besseren Information des Lesers aufgenommen. Die Liste ist nicht Bestandteil der deutschen Patent- bzw. Gebrauchsmusteranmeldung. Das DPMA übernimmt keinerlei Haftung für etwaige Fehler oder Auslassungen.This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Zitierte PatentliteraturCited patent literature

  • US 8753883 B [0010]US 8753883 B [0010]
  • WO 2017062475 A [0011]WO 2017062475 A [0011]

Zitierte Nicht-PatentliteraturCited non-patent literature

  • Rivas Bejarano JJ, Valdecantos WC. Psoriasis as autoinflammatory disease. Dermatol Clin. 2013 Jul;31(3):445- 60 [0013]Rivas Bejarano JJ, Valdecantos WC. Psoriasis as autoinflammatory disease. Dermatol Clin. 2013 Jul; 31 (3): 445-60 [0013]
  • Lowes MA, Suárez- Fariñas M, Krueger JG. Immunology of psoriasis. AnnuAnnu Rev Immunol. 2014; 32: 227- 55 [0013]Lowes MA, Suárez-Fariñas M, Krueger JG. Immunology of psoriasis. AnnuAnnu Rev Immunol. 2014; 32: 227-55 [0013]
  • Lauren Y. Cao, Jin-Sung Chung, Takahiro Teshima, Lawrence Feigenbaum, Ponciano D. Cruz, Jr., Heidi T. Jacobe, Benjamin F. Chong, and Kiyoshi Ariizumi. Myeloid- derived Suppressor Cells in Psoriasis are an Expanded Population Exhibiting Diverse T cell- Suppressor Mechanisms. J Invest Dermatol. 2016; 136(9): 1801-1810 [0013]Lauren Y. Cao, Jin-Sung Chung, Takahiro Teshima, Lawrence Feigenbaum, Ponciano D. Cruz, Jr., Heidi T. Jacobe, Benjamin F. Chong, and Kiyoshi Ariizumi. Myeloid-derived Suppressor Cells in Psoriasis are Expanded Population Exhibiting Diverse T cell Suppressor Mechanisms. J Invest Dermatol. 2016; 136 (9): 1801-1810 [0013]
  • Zeng R, Wang LW, Hu ZB, Guo WT, Wei JS, Lin H, et al. Differentiation of human bone marrow mesenchymal stem cells into neuron- like cells in vitro. Spine (Phila Pa 1976) 2011;36:997- 1005 [0013]Zeng R, Wang LW, Hu ZB, Guo WT, Wei JS, Lin H, et al. Differentiation of human bone marrow mesenchymal stem cells into neuron-like cells in vitro. Spine (Phila Pa 1976) 2011; 36: 997-1005 [0013]
  • Salgado AJ, Sousa JC, Costa BM, Pires AO, Mateus- Pinheiro A, Teixeira FG, et al. Mesenchymal stem cells secretome as a modulator of the neurogenic niche: basic insights and therapeutic opportunities. Front Cell Neurosci 2015;9:249 [0013]Salgado AJ, Sousa JC, Costa BM, Pires AO, Mateus-Pinheiro A, Teixeira FG, et al. Mesenchymal stem cells secretome as a modulator of neurogenic diseases: basic insights and therapeutic opportunities. Front Cell Neurosci 2015; 9: 249 [0013]
  • Ben- Ami E, Berrih- Aknin S, Miller A. Mesenchym al stem cells as an immunomodulatory therapeutic strategy for autoimmune diseases. Autoimmun Rev 2011;10:410-5 [0013]Ben-Ami E, Berrih-Aknin S, Miller A. Mesenchymal stem cells as an immunomodulatory therapeutic strategy for autoimmune diseases. Autoimmune Rev 2011; 10: 410-5 [0013]
  • Kyurkchiev D, Bochev I, Ivanova- Todorova E, Mourdjeva M, Oreshkova T, Belemezova K, Kyurkchiev S. Secretion of immunoregulatory cytokines by mesenchymal stem cells. World J Stem Cells 2014;6:552-70 [0013]Kyurkchiev D, Bochev I, Ivanova- Todorova E, Mourdjeva M, Oreshkova T, Belemezova K, Kyurkchiev S. Secretion of immunoregulatory cytokines by mesenchymal stem cells. World J Stem Cells 2014; 6: 552-70 [0013]
  • Mendez- Samperio P, Garcia E, Vázquez A, Palma J. Regulation of Interleukin- 8 by Interleukin-10 and Transforming Growth Factor in β Human Monocytes Infected with Mycobacterium bovis. Clin Diagn Lab Immunol 2002;9:802-70 [0013]Mendez-Samperio P, Garcia E, Vázquez A, Palma J. Regulation of Interleukin-8 by Interleukin-10 and Transforming Growth Factor in β Human Monocytes Infected with Mycobacterium bovis. Clin Diagn Lab Immunol 2002; 9: 802-70 [0013]
  • Fabry Z, Topham DJ, Fee D, Herlein J, Carlino JA, Hart MN, Sriram S. TGF- beta 2 decreas e s migration of lymphocytes in vitro and homing of cells into the central nervous system in vivo. J Immunol 1995;155:325-32 [0013]Fabry Z, Topham DJ, Fee D, Herlein J, Carlino JA, Hart MN, Sriram S. TGF-beta 2, the migration of lymphocytes in vitro and homing of cells into the central nervous system in vivo. J Immunol 1995; 155: 325-32 [0013]
  • Agard M, Asakrah S, Morici LA. PGE2 suppres sion of innate immunity during mucosal bacterial infection. Front Cell Infect Microbiol 2013;3:45 [0013]Agard M, Asakrah S, Morici LA. PGE2 suppression of innate immunity during mucosal bacterial infection. Front Cell Infect Microbiol 2013; 3: 45 [0013]
  • Duffy AM, Bouchier- Hayes DJ, Harmey JH. Vascular Endothelial Growthr (VEGF) and Its Role in Non- Endothelial Cells: Autocrine Signalling by VEGF. In: Madam e Curie Bioscience Databas e (Interne t). Austin (TX): Landes Bioscience; 2000-2013 [0013]Duffy AM, Boucher-Hayes DJ, Harmey JH. Vascular Endothelial Growthr (VEGF) and Its Role in Non-Endothelial Cells: Autocrine Signaling by VEGF. In: Madame e Curie Bioscience Databas e (Interne t). Austin (TX): Landes Bioscience; 2000-2013 [0013]
  • Baksh D, Yao R, Tuan RS. Comparison of Proliferative and Multilineage Differentiation Potential of Human Mesenchymal Stem Cells Derived from Umbilical Cord and Bone Marrow. Stem Cells 2007;25:1384-92. https://doi.org/10.1634/ stemcells.2006- 0709 [0013]Baksh D, Yao R, Tuan RS. Comparison of Proliferative and Multilineage Differentiation Potential of Human Mesenchymal Stem Cells Derived from Umbilical Cord and Bone Marrow. Stem Cells 2007; 25: 1384-92. https://doi.org/10.1634/ stemcells.2006-0709 [0013]
  • LIU, Y. and WILLIAMS, D.J. Processing of collagen gels to create in vitro cell growth matrix without damage to the collagen native structure. Proceedings of the Institution of Mechanical Engineers, Part B: Journal of Engineering Manufacture, 2006; 220 (5), pp. 787- 791 [0013]LIU, Y. and WILLIAMS, D.J. Processing collagen gels to create in vitro cell growth matrix without damage to the collagen native structure. Proceedings of the Institution of Mechanical Engineers, Part B: Journal of Engineering Manufacture, 2006; 220 (5), pp. 787-791 [0013]

Claims (2)

Die in vitro Erzeugung von Knochenmark- MSCs in Kollagengel Kulture, das für Hautanwendung bei Psoriasis und ähnliche Läsionen appliziert werden kann.The in vitro production of bone marrow MSCs in collagen gel culture, which can be applied for skin application in psoriasis and similar lesions. Das Kollagengel wird dadurch mit den Mediatoren geflutet, die von den Zellen sekretiert werden. Mit rechtzeitiger korrekter und wiederholter Anwendung solches Gels auf den psoriatischen Läsionen wird es erwartet, dass eine hochgradige T-Zell-Hemmung und Anti-Autoimmunaktivität erreicht werden.The collagen gel is thereby flooded with the mediators that are secreted by the cells. Timely correct and repeated application of such gel to the psoriatic lesions is expected to result in high level T cell inhibition and anti-autoimmune activity.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116725948A (en) * 2023-07-14 2023-09-12 黑龙江八一农垦大学 Adipose-derived stem cell-mediated gel and preparation method and application thereof

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US8753883B2 (en) 2002-02-13 2014-06-17 Anthrogenesis Corporation Treatment of psoriasis using placental stem cells
WO2017062475A1 (en) 2015-10-05 2017-04-13 The Regents Of The University Of California Use of mesenchymal stem cells for the treatment of inflammation

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8753883B2 (en) 2002-02-13 2014-06-17 Anthrogenesis Corporation Treatment of psoriasis using placental stem cells
WO2017062475A1 (en) 2015-10-05 2017-04-13 The Regents Of The University Of California Use of mesenchymal stem cells for the treatment of inflammation

Non-Patent Citations (13)

* Cited by examiner, † Cited by third party
Title
Agard M, Asakrah S, Morici LA. PGE2 suppres sion of innate immunity during mucosal bacterial infection. Front Cell Infect Microbiol 2013;3:45
Baksh D, Yao R, Tuan RS. Comparison of Proliferative and Multilineage Differentiation Potential of Human Mesenchymal Stem Cells Derived from Umbilical Cord and Bone Marrow. Stem Cells 2007;25:1384-92. https://doi.org/10.1634/ stemcells.2006- 0709
Ben- Ami E, Berrih- Aknin S, Miller A. Mesenchym al stem cells as an immunomodulatory therapeutic strategy for autoimmune diseases. Autoimmun Rev 2011;10:410-5
Duffy AM, Bouchier- Hayes DJ, Harmey JH. Vascular Endothelial Growthr (VEGF) and Its Role in Non- Endothelial Cells: Autocrine Signalling by VEGF. In: Madam e Curie Bioscience Databas e (Interne t). Austin (TX): Landes Bioscience; 2000-2013
Fabry Z, Topham DJ, Fee D, Herlein J, Carlino JA, Hart MN, Sriram S. TGF- beta 2 decreas e s migration of lymphocytes in vitro and homing of cells into the central nervous system in vivo. J Immunol 1995;155:325-32
Kyurkchiev D, Bochev I, Ivanova- Todorova E, Mourdjeva M, Oreshkova T, Belemezova K, Kyurkchiev S. Secretion of immunoregulatory cytokines by mesenchymal stem cells. World J Stem Cells 2014;6:552-70
Lauren Y. Cao, Jin-Sung Chung, Takahiro Teshima, Lawrence Feigenbaum, Ponciano D. Cruz, Jr., Heidi T. Jacobe, Benjamin F. Chong, and Kiyoshi Ariizumi. Myeloid- derived Suppressor Cells in Psoriasis are an Expanded Population Exhibiting Diverse T cell- Suppressor Mechanisms. J Invest Dermatol. 2016; 136(9): 1801-1810
LIU, Y. and WILLIAMS, D.J. Processing of collagen gels to create in vitro cell growth matrix without damage to the collagen native structure. Proceedings of the Institution of Mechanical Engineers, Part B: Journal of Engineering Manufacture, 2006; 220 (5), pp. 787- 791
Lowes MA, Suárez- Fariñas M, Krueger JG. Immunology of psoriasis. AnnuAnnu Rev Immunol. 2014; 32: 227- 55
Mendez- Samperio P, Garcia E, Vázquez A, Palma J. Regulation of Interleukin- 8 by Interleukin-10 and Transforming Growth Factor in β Human Monocytes Infected with Mycobacterium bovis. Clin Diagn Lab Immunol 2002;9:802-70
Rivas Bejarano JJ, Valdecantos WC. Psoriasis as autoinflammatory disease. Dermatol Clin. 2013 Jul;31(3):445- 60
Salgado AJ, Sousa JC, Costa BM, Pires AO, Mateus- Pinheiro A, Teixeira FG, et al. Mesenchymal stem cells secretome as a modulator of the neurogenic niche: basic insights and therapeutic opportunities. Front Cell Neurosci 2015;9:249
Zeng R, Wang LW, Hu ZB, Guo WT, Wei JS, Lin H, et al. Differentiation of human bone marrow mesenchymal stem cells into neuron- like cells in vitro. Spine (Phila Pa 1976) 2011;36:997- 1005

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116725948A (en) * 2023-07-14 2023-09-12 黑龙江八一农垦大学 Adipose-derived stem cell-mediated gel and preparation method and application thereof
CN116725948B (en) * 2023-07-14 2024-03-26 黑龙江八一农垦大学 Adipose-derived stem cell-mediated gel and preparation method and application thereof

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