ES2573522T3 - Composiciones y métodos para el trasplante celular - Google Patents
Composiciones y métodos para el trasplante celular Download PDFInfo
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- ES2573522T3 ES2573522T3 ES12704242.2T ES12704242T ES2573522T3 ES 2573522 T3 ES2573522 T3 ES 2573522T3 ES 12704242 T ES12704242 T ES 12704242T ES 2573522 T3 ES2573522 T3 ES 2573522T3
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- cells
- hirudin
- bivaliriduna
- heparin
- fondaparinux
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- 239000000203 mixture Substances 0.000 title description 8
- 238000002054 transplantation Methods 0.000 title description 5
- 238000000034 method Methods 0.000 title description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 abstract description 38
- 229920000669 heparin Polymers 0.000 abstract description 31
- 210000004027 cell Anatomy 0.000 abstract description 30
- 108010007267 Hirudins Proteins 0.000 abstract description 26
- 102000007625 Hirudins Human genes 0.000 abstract description 26
- 229940006607 hirudin Drugs 0.000 abstract description 26
- WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 abstract description 26
- KANJSNBRCNMZMV-ABRZTLGGSA-N fondaparinux Chemical compound O[C@@H]1[C@@H](NS(O)(=O)=O)[C@@H](OC)O[C@H](COS(O)(=O)=O)[C@H]1O[C@H]1[C@H](OS(O)(=O)=O)[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O[C@@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O4)NS(O)(=O)=O)[C@H](O3)C(O)=O)O)[C@@H](COS(O)(=O)=O)O2)NS(O)(=O)=O)[C@H](C(O)=O)O1 KANJSNBRCNMZMV-ABRZTLGGSA-N 0.000 abstract description 13
- 229960001318 fondaparinux Drugs 0.000 abstract description 13
- 229960002897 heparin Drugs 0.000 abstract description 13
- 230000002440 hepatic effect Effects 0.000 abstract description 12
- 210000000651 myofibroblast Anatomy 0.000 abstract description 11
- 210000000130 stem cell Anatomy 0.000 abstract description 11
- 101000712605 Theromyzon tessulatum Theromin Proteins 0.000 abstract description 3
- 229940122388 Thrombin inhibitor Drugs 0.000 abstract description 3
- 108010055460 bivalirudin Proteins 0.000 abstract description 3
- 229960001500 bivalirudin Drugs 0.000 abstract description 3
- OIRCOABEOLEUMC-GEJPAHFPSA-N bivalirudin Chemical group C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 OIRCOABEOLEUMC-GEJPAHFPSA-N 0.000 abstract description 3
- 239000003868 thrombin inhibitor Substances 0.000 abstract description 3
- 239000012190 activator Substances 0.000 abstract 2
- 239000004019 antithrombin Substances 0.000 abstract 2
- 239000003055 low molecular weight heparin Substances 0.000 abstract 1
- 229940127215 low-molecular weight heparin Drugs 0.000 abstract 1
- 210000004185 liver Anatomy 0.000 description 11
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 10
- 210000001185 bone marrow Anatomy 0.000 description 9
- 210000002950 fibroblast Anatomy 0.000 description 9
- 239000003805 procoagulant Substances 0.000 description 9
- 239000000126 substance Substances 0.000 description 4
- 230000006727 cell loss Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229960000610 enoxaparin Drugs 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 229940090880 ardeparin Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229940107792 certoparin Drugs 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000002338 cryopreservative effect Effects 0.000 description 1
- 229960004969 dalteparin Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229960000899 nadroparin Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229960004762 parnaparin Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002947 procoagulating effect Effects 0.000 description 1
- 229960005496 reviparin Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 229960005062 tinzaparin Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/727—Heparin; Heparan
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
-
- 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
- A61K35/37—Digestive system
- A61K35/407—Liver; Hepatocytes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/55—Protease inhibitors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/55—Protease inhibitors
- A61K38/57—Protease inhibitors from animals; from humans
- A61K38/58—Protease inhibitors from animals; from humans from leeches, e.g. hirudin, eglin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- A—HUMAN NECESSITIES
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- 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
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- Medicinal Chemistry (AREA)
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- Developmental Biology & Embryology (AREA)
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- Gastroenterology & Hepatology (AREA)
- Biotechnology (AREA)
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- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract
Una combinacion que comprende al menos un activador de antitrombina, al menos un inhibidor de la trombina y celulas seleccionadas entre el grupo que consiste en celulas progenitoras hepaticas adultas y miofibroblastos hepaticos, en la que: - el activador de antitrombina se selecciona entre el grupo que consiste en heparina, heparina no fraccionada, heparina de bajo peso molecular y fondaparinux; y - el inhibidor de la trombina se selecciona entre el grupo que consiste en bivalirudina e hirudina.
Description
heparina no fraccionada, un inhibidor de la trombina seleccionado entre el grupo que consiste en bivalirudina e hirudina, preferentemente bivalirudina, y células seleccionadas opcionalmente entre el grupo que consiste en células progenitoras hepáticas adultas, células madre mesenquimales (preferentemente células madre mesenquimales de médula ósea), fibroblastos cutáneos, o miofibroblastos hepáticos, preferentemente células progenitoras hepáticas
5 adultas o miofibroblastos hepáticos, más preferentemente células progenitoras hepáticas adultas.
Otras combinaciones o composiciones particularmente preferentes que incorporan los principios de la invención se desvelan en la Tabla 1, es decir, combinaciones o composiciones que comprenden, que consisten esencialmente, o consisten en la sustancia 1, sustancia 2, y opcionalmente células.
10 Tabla 1
- sustancia 1
- sustancia 2 células
- heparina
- hirudina
- heparina
- bivaliriduna
- heparina no fraccionada
- hirudina
- heparina no fraccionada
- bivaliriduna
- HBPM1
- hirudina
- HBPM1
- bivaliriduna
- fondaparinux
- hirudina
- fondaparinux
- bivaliriduna
- heparina
- hirudina células procoagulantes
- heparina
- bivaliriduna células procoagulantes
- heparina no fraccionada
- hirudina células procoagulantes
- heparina no fraccionada
- bivaliriduna células procoagulantes
- HBPM1
- hirudina células procoagulantes
- HBPM1
- bivaliriduna células procoagulantes
- fondaparinux
- hirudina células procoagulantes
- fondaparinux
- bivaliriduna células procoagulantes
- heparina
- hirudina células progenitoras hepáticas adultas
- heparina
- bivaliriduna células progenitoras hepáticas adultas
- heparina no fraccionada
- hirudina células progenitoras hepáticas adultas
- heparina no fraccionada
- bivaliriduna células progenitoras hepáticas adultas
- HBPM1
- hirudina células progenitoras hepáticas adultas
- HBPM1
- bivaliriduna células progenitoras hepáticas adultas
- fondaparinux
- hirudina células progenitoras hepáticas adultas
- fondaparinux
- bivaliriduna células progenitoras hepáticas adultas
- heparina
- hirudina células madre mesenquimales (médula ósea)
- heparina
- bivaliriduna células madre mesenquimales (médula ósea)
- heparina no fraccionada
- hirudina células madre mesenquimales (médula ósea)
- heparina no fraccionada
- bivaliriduna células madre mesenquimales (médula ósea)
- HBPM1
- hirudina células madre mesenquimales (médula ósea)
- HBPM1
- bivaliriduna células madre mesenquimales (médula ósea)
- fondaparinux
- hirudina células madre mesenquimales (médula ósea)
17
- fondaparinux
- bivaliriduna células madre mesenquimales (médula ósea)
- heparina
- hirudina fibroblastos cutáneos
- heparina
- bivaliriduna fibroblastos cutáneos
- heparina no fraccionada
- hirudina fibroblastos cutáneos
- heparina no fraccionada
- bivaliriduna fibroblastos cutáneos
- HBPM1
- hirudina fibroblastos cutáneos
- HBPM1
- bivaliriduna fibroblastos cutáneos
- fondaparinux
- hirudina fibroblastos cutáneos
- fondaparinux
- bivaliriduna fibroblastos cutáneos
- heparina
- hirudina miofibroblastos hepáticos
- heparina
- bivaliriduna miofibroblastos hepáticos
- heparina no fraccionada
- hirudina miofibroblastos hepáticos
- heparina no fraccionada
- bivaliriduna miofibroblastos hepáticos
- HBPM1
- hirudina miofibroblastos hepáticos
- HBPM1
- bivaliriduna miofibroblastos hepáticos
- fondaparinux
- hirudina miofibroblastos hepáticos
- fondaparinux
- bivaliriduna miofibroblastos hepáticos
- 1 HBPM incluye ardeparina, certoparina, enoxaparina, parnaparina, tinzaparina, dalteparina, reviparina y nadroparina, preferentemente HBPM es enoxaparina.
El término "trasplante celular" conlleva su significado normal y en particular se refiere a la administración de células a un sujeto. El término "trasplante celular" se puede emplear indistintamente con "terapia celular". El trasplante celular puede realizarse por medio de cualquier técnica conocida en la materia. A modo de ejemplo, y sin limitación, las 5 células pueden trasplantarse por infusión en un sujeto. Normalmente, la infusión de células puede llevarse a cabo parenteralmente, p. ej., por vía intravascular, subcutánea, intradérmica, o intramuscular, preferentemente por vía intravascular. Las células pueden administrarse, por ejemplo, entre otros, por vía sistémica, tópica o en el sitio de una lesión. En consecuencia, puede resultar evidente que, en función de la aplicación específica, los tejidos diana, el fin terapéutico o el tipo celular, puede realizarse un ajuste en relación a las vías de administración, así como
10 formulaciones, concentraciones, etc.
Como se utiliza en el presente documento, el término "complicaciones trombóticas" o "complicaciones procoagulantes" puede referirse particularmente a efectos deletéreos o complicaciones asociadas con el trasplante de células con actividad procoagulante, aparte de la formación de coágulos per se. Dichos efectos pueden ser, por 15 ejemplo, entre otros, pérdida celular, rechazo celular o inflamación. Por pérdida celular o rechazo celular se entiende la pérdida o el rechazo de las células trasplantadas. El resultado de estos efectos es una disminución de la eficacia en el trasplante de células o posible prendimiento celular, inferior a, o en casos extremos, ninguna cantidad total administrada de las células está disponible para realizar su función prevista tras el trasplante. La pérdida de células puede ocurrir por ejemplo debido a la inclusión de las células trasplantadas en coágulos. El rechazo celular puede
20 por ejemplo ocurrir debido a una respuesta inmunológica del huésped. Una respuesta inflamatoria puede por ejemplo asociarse, o ser resultado de la activación de la cascada de coagulación. Alternativamente, o además, la inflamación puede asociarse con, o ser resultado de, o causar rechazo celular.
Se proporcionan igualmente composiciones que comprenden las combinaciones enseñadas en el presente
25 documento y que comprenden además uno o varios componentes. Por ejemplo, los componentes que pueden incluirse pueden mantener o mejorar la viabilidad de las células. Como ejemplo y sin limitación, tales componentes pueden incluir sales para garantizar sustancialmente condiciones isotónicas, estabilizadores del pH tales como sistema(s) tampón (p. ej., para garantizar un pH sustancialmente neutro, tal como el sistema tampón fosfato o carbonato), proteínas transportadoras, tales como por ejemplo albúmina, medios que incluyen medios basales y/o
30 suplementos de medios, suero o plasma, nutrientes, fuentes de carbohidratos, conservantes, estabilizadores, antioxidantes u otros materiales adecuadamente conocidos por los expertos en la materia. Asimismo se desvelan métodos de producción de dichas composiciones mezclando los respectivos componentes de las combinaciones enseñadas en el presente documento con dichos o más componentes adicionales indicados. Las composiciones pueden ser, por ejemplo líquidas o pueden ser semisólidas o sólidas (p. ej., pueden ser composiciones congeladas o
35 pueden existir como geles o existir en el apoyo o armazón sólido, etc.). Los crioconservantes, tales como, inter alia,
18
Claims (1)
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| EP11152119 | 2011-01-25 | ||
| PCT/EP2012/051157 WO2012101181A1 (en) | 2011-01-25 | 2012-01-25 | Compositions and methods for cell transplantation |
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| WO2012101181A1 (en) | 2011-01-25 | 2012-08-02 | Université Catholique de Louvain | Compositions and methods for cell transplantation |
| ES2726802T3 (es) | 2012-01-25 | 2019-10-09 | Univ Catholique Louvain | Composiciones y métodos para el trasplante celular |
| JP6525889B2 (ja) * | 2013-01-12 | 2019-06-05 | セスカ セラピューティクス， インコーポレイテッド | 自己骨髄由来の幹細胞の迅速な注入 |
| SG11201507620VA (en) | 2013-03-15 | 2015-10-29 | Miromatrix Medical Inc | Use of perfusion decellularized liver for islet cell recellularization |
| DK3016665T3 (da) | 2013-07-05 | 2019-11-25 | Univ Catholique Louvain | Konditioneret medium fra humane voksne leverstamceller og dets anvendelse i behandlingen af leverlidelser |
| BR102013033827B1 (pt) * | 2013-12-27 | 2021-09-08 | Regenera - Medicina Veterinária Avançada Ltda. | Concentrado multipotente e imunocompatível de células-tronco e biofármaco e forma de dosagem que o compreendem |
| EP3307279B1 (en) * | 2015-06-11 | 2019-12-04 | Universiteit Maastricht | Method for preventing transplant failure in a host. |
| CN106995796A (zh) * | 2016-01-26 | 2017-08-01 | 李建业 | 基于细胞因子的细胞处理方法、试剂盒及冻干粉 |
| WO2018159431A1 (ja) | 2017-03-03 | 2018-09-07 | ロート製薬株式会社 | 間葉系幹細胞及び肝疾患治療剤 |
| WO2018231726A1 (en) * | 2017-06-12 | 2018-12-20 | The University Of North Carolina At Chapel Hill | Patch graft compositions for cell engraftment |
| JP7264589B2 (ja) * | 2017-12-25 | 2023-04-25 | 株式会社 資生堂 | トロンビンの抑制作用を指標とした皮膚状態改善剤のスクリーニング方法、及びトロンビン作用阻害剤を含む皮膚状態改善剤 |
| CN112608890B (zh) * | 2020-12-17 | 2024-08-20 | 山东佰鸿干细胞生物技术有限公司 | 一种防止间充质干细胞粘连的培养方法 |
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| GB9010552D0 (en) | 1990-05-10 | 1990-07-04 | Erba Carlo Spa | Method for the recombinant production of hirudins and novel hirudins |
| US5811094A (en) | 1990-11-16 | 1998-09-22 | Osiris Therapeutics, Inc. | Connective tissue regeneration using human mesenchymal stem cell preparations |
| US5837539A (en) | 1990-11-16 | 1998-11-17 | Osiris Therapeutics, Inc. | Monoclonal antibodies for human mesenchymal stem cells |
| US5486359A (en) | 1990-11-16 | 1996-01-23 | Osiris Therapeutics, Inc. | Human mesenchymal stem cells |
| US5843780A (en) | 1995-01-20 | 1998-12-01 | Wisconsin Alumni Research Foundation | Primate embryonic stem cells |
| US5736396A (en) | 1995-01-24 | 1998-04-07 | Case Western Reserve University | Lineage-directed induction of human mesenchymal stem cell differentiation |
| US5827740A (en) | 1996-07-30 | 1998-10-27 | Osiris Therapeutics, Inc. | Adipogenic differentiation of human mesenchymal stem cells |
| GB0014136D0 (en) | 2000-06-10 | 2000-08-02 | Astrazeneca Ab | Combination therapy |
| DE10202982A1 (de) | 2002-01-26 | 2003-07-31 | Augustinus Bader | Verfahren und Vorrichtung zum Einbringen von lebenden Zellen in eine biologische Körperflüssigkeit |
| US20060222640A1 (en) * | 2005-03-29 | 2006-10-05 | Boehringer Ingelheim International Gmbh | New pharmaceutical compositions for treatment of thrombosis |
| WO2006126219A1 (en) | 2005-05-26 | 2006-11-30 | Fresenius Medical Care Deutschland G.M.B.H. | Liver progenitor cells |
| JP2009508650A (ja) * | 2005-09-21 | 2009-03-05 | ダスク テクノロジーズ， エルエルシー | 臓器および組織機能のための方法および組成 |
| WO2007071339A1 (en) * | 2005-12-21 | 2007-06-28 | Universite Catholique De Louvain | Isolated liver stem cells |
| WO2012101181A1 (en) | 2011-01-25 | 2012-08-02 | Université Catholique de Louvain | Compositions and methods for cell transplantation |
| ES2726802T3 (es) | 2012-01-25 | 2019-10-09 | Univ Catholique Louvain | Composiciones y métodos para el trasplante celular |
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| US10039789B2 (en) | 2018-08-07 |
| US20130302291A1 (en) | 2013-11-14 |
| US20170042940A1 (en) | 2017-02-16 |
| JP2014508138A (ja) | 2014-04-03 |
| CN103402527B (zh) | 2016-04-20 |
| JP6012629B2 (ja) | 2016-10-25 |
| WO2012101181A1 (en) | 2012-08-02 |
| EP2667878A1 (en) | 2013-12-04 |
| CA2825252C (en) | 2018-10-16 |
| EP2667878B1 (en) | 2016-03-30 |
| CN103402527A (zh) | 2013-11-20 |
| US10478459B2 (en) | 2019-11-19 |
| DK2667878T3 (en) | 2016-06-27 |
| SG192124A1 (en) | 2013-08-30 |
| US20170354723A1 (en) | 2017-12-14 |
| CA2825252A1 (en) | 2012-08-02 |
| PL2667878T3 (pl) | 2016-10-31 |
| PT2667878E (pt) | 2016-06-03 |
| IL227529A0 (en) | 2013-09-30 |
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