CN101415817B - 截留干细胞及其使用 - Google Patents
截留干细胞及其使用 Download PDFInfo
- Publication number
- CN101415817B CN101415817B CN200480023971.2A CN200480023971A CN101415817B CN 101415817 B CN101415817 B CN 101415817B CN 200480023971 A CN200480023971 A CN 200480023971A CN 101415817 B CN101415817 B CN 101415817B
- Authority
- CN
- China
- Prior art keywords
- cell
- agarose
- stem cell
- stem
- purposes
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 210000000130 stem cell Anatomy 0.000 title claims abstract description 92
- 210000004027 cell Anatomy 0.000 claims abstract description 122
- 238000000034 method Methods 0.000 claims abstract description 31
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 23
- 201000011510 cancer Diseases 0.000 claims abstract description 21
- 230000004069 differentiation Effects 0.000 claims abstract description 13
- 210000001671 embryonic stem cell Anatomy 0.000 claims abstract description 8
- 230000008569 process Effects 0.000 claims abstract description 8
- 230000003463 hyperproliferative effect Effects 0.000 claims abstract description 6
- 229920000936 Agarose Polymers 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 20
- 241000894007 species Species 0.000 claims description 12
- 208000005623 Carcinogenesis Diseases 0.000 claims description 4
- 241001529936 Murinae Species 0.000 claims description 4
- 230000036952 cancer formation Effects 0.000 claims description 4
- 231100000504 carcinogenesis Toxicity 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 230000005764 inhibitory process Effects 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 102000008186 Collagen Human genes 0.000 claims description 2
- 108010035532 Collagen Proteins 0.000 claims description 2
- 108010010803 Gelatin Proteins 0.000 claims description 2
- 229920001436 collagen Polymers 0.000 claims description 2
- 239000008273 gelatin Substances 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 235000011852 gelatine desserts Nutrition 0.000 claims description 2
- 238000007599 discharging Methods 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 28
- 230000001613 neoplastic effect Effects 0.000 abstract description 2
- 230000035755 proliferation Effects 0.000 abstract 3
- 230000007774 longterm Effects 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
- 208000035475 disorder Diseases 0.000 description 9
- 239000002609 medium Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 230000004663 cell proliferation Effects 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 208000017733 acquired polycythemia vera Diseases 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 230000035764 nutrition Effects 0.000 description 3
- 235000016709 nutrition Nutrition 0.000 description 3
- 208000030761 polycystic kidney disease Diseases 0.000 description 3
- 208000037244 polycythemia vera Diseases 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 2
- 241000529895 Stercorarius Species 0.000 description 2
- 229940072056 alginate Drugs 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- PGSADBUBUOPOJS-UHFFFAOYSA-N neutral red Chemical compound Cl.C1=C(C)C(N)=CC2=NC3=CC(N(C)C)=CC=C3N=C21 PGSADBUBUOPOJS-UHFFFAOYSA-N 0.000 description 2
- 210000001915 nurse cell Anatomy 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 230000003313 weakening effect Effects 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
- -1 Poly-hydroxyl ethane Chemical compound 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000000560 biocompatible material Substances 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 239000003519 biomedical and dental material Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- NCEXYHBECQHGNR-UHFFFAOYSA-N chembl421 Chemical compound C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000009415 formwork Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 210000000087 hemolymph Anatomy 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 210000004332 phalangeal cell Anatomy 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- 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
- C12N5/0693—Tumour cells; Cancer cells
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0205—Chemical aspects
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0205—Chemical aspects
- A01N1/0231—Chemically defined matrices, e.g. alginate gels, for immobilising, holding or storing cells, tissue or organs for preservation purposes; Chemically altering or fixing cells, tissue or organs, e.g. by cross-linking, for preservation purposes
-
- 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
- A61K35/13—Tumour cells, irrespective of tissue of origin
-
- 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
- A61K35/54—Ovaries; Ova; Ovules; Embryos; Foetal cells; Germ cells
- A61K35/545—Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- 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
- C12N5/0012—Cell encapsulation
-
- 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
-
- 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
- C12N5/0603—Embryonic cells ; Embryoid bodies
- C12N5/0606—Pluripotent embryonic cells, e.g. embryonic stem cells [ES]
-
- 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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/02—Coculture with; Conditioned medium produced by embryonic cells
-
- 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
- C12N2533/70—Polysaccharides
- C12N2533/76—Agarose, agar-agar
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cell Biology (AREA)
- Developmental Biology & Embryology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Reproductive Health (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Gynecology & Obstetrics (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Environmental Sciences (AREA)
- Immunology (AREA)
- Dentistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Dispersion Chemistry (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明涉及干细胞,特别是胚胎干细胞。发现当截留这些干细胞时,其增殖被抑制,其生成抑制其它、非截留细胞,包括干细胞和瘤形成和/或过度增殖但不同于正常细胞的细胞增殖的物质。还发现截留的癌细胞将生成抑制干细胞增殖的物质。另外,还发现干细胞的截留抑制它们的分化并且因此截留方法可作为维持至少部分截留细胞处于未分化状态的长期存储方法。
Description
发明领域
本发明涉及诸如干细胞的截留细胞。当该截留细胞在截留材料中培养时,生成一种产物,当该产物与其它非截留的,自由生长的细胞在体外或体内接触时,抑制其增殖。此外,干细胞的截留起抑制至少一些截留干细胞的增殖的作用,并且可以抑制至少部分截留干细胞的分化。
发明背景和先前技术
诸如细胞的生物材料的截留是已经被用于多种目标的技术。该领域的专利文献的实例如6,303,151(Asina等);6,224,912(Asina等);5,888,497(Jain等);5,643,569(Jain等);和RE38,027(Jain等)等美国专利,所有这些通过引用而全部并入本文。该组相关专利显示癌症细胞和胰岛(islets)可以被截留在生物适合的基质中,例如琼脂糖、琼脂糖/胶原混合物和琼脂糖/明胶混合物,并且然后用琼脂糖包被。所得的截留细胞生成多种物质,这些物质与其他物质还从保留其的可渗透的生物适合材料中扩散出来,并具有有用的生物特性。在胰岛的情况中,生成胰岛素。在癌症细胞的情况中,物质从基质中扩散出来,并且该物质对癌症细胞的生长和增殖具有影响作用。如上文引用的‘912和‘151专利的评论显示该作用跨越物种,即,从一个给定的物种来的截留的或被包围的癌细胞产生的物质可抑制来自其它物种的癌细胞以及产生该癌细胞的物种的癌细胞的生长和/或增殖。
截留技术其它的实例包括,例如专利号为5,227,298(Weber等);5,053,332(Cook等);4,997,443(Walthall等);4,971,833(Larsson等);4,902,295(Walthall等);4,798,786(Tice等);4,673,566(Goosen等);4,647,536(Mosbach等);4,409,331(Lim);4,392,909(Lim);4,352,883(Lim)和4,663,286(Tsang等)的美国专利。所有这些文献通过引用而并入本文。
截留并不总是对截留细胞产生积极的作用。例如,参见Lloyd-Gerorge等,Biomat.Art.Cells & Immob.Biotech.,21(3):323-333(1993);Schinstine等,Cell Transplant,41(1):93-102(1995);Chicheportiche等,Diabetologica,31:54-57(1988);Jaeger等,Progress InBrain Research,82:41-46(1990);Zekorn等,Diabetologica,29:99-106(1992);Zhou等,Am.J.Physiol.,274:C1356-1362(1998);Darquy等,Diabetologica,28:776-780(1985);Tse等,Biotech.& Bioeng.,51:271-280(1996):Jaeger等,J.Neurol.,21-469-480(1992);Hortelano等,Blood,87(12):5095-5103(1996):Gardiner等,Transp.Proc.,29:2019-2020(1997)。所有这些文献通过引用而并入本文。
上述的文献没有一个涉及已知为干细胞,包括胚胎干细胞的细胞种类。
由Reya等,在Nature,414:105-111(2001)中提出的一个干细胞的定义通过引用而并入本文,指出干细胞是具有通过自我更新而可以使其永久化的能力,并且通过分化而产生特定组织的成熟细胞的细胞。可以获得不同类型的干细胞,包括神经、血淋巴(hematolymphoid)、骨髓的以及来自于不同器官的其它类型的干细胞。这些都具有发育成特定器官或组织的潜力。一定的干细胞,例如胚胎干细胞,是多能性的,其分化途径没有任何的限制,并且其可以发育成各种器官和组织。
关于可以将干细胞用于多种治疗用途中的讨论已是众所周知,这里不需要再进行讨论。由于其适合于本文描述的发明,值得提及的是,干细胞是非常难得的,从其它细胞类型中分离和纯化是费力和困难的,而且,除非用一定的方式处理,否则干细胞将分化为成熟细胞。
已经发现,符合Jain等和Iwata等在Journ.Biomedical Material andRes.,26:967(1992)中披露的截留操作以期望的方式影响干细胞。为了详细阐述,截留干细胞生成抑制包括干细胞和癌细胞的多种细胞类型的增殖的物质。此物质的作用跨越种系。而且,发现当如本文描述的截留干细胞时,它们的分化能力,包括其多潜能性被保留了不确定的时间。
这些特性以及其它将要在下文中披露。
优选实施方案的详细描述
实施例1
从美国菌种保藏中心(ATCC)获得两个不同鼠胚胎干细胞系(ES),即ES-D3和SCC-PSA1,其均可被公众获得。
两个细胞系均在标准的培养条件下生长,包括在“STO”胚胎纤维原细胞滋养细胞上以单层生长。这些细胞也从ATCC获得。干细胞在补充有100%ES-级(ES-Qualified)胎牛血清,白血病抑制因子(LIF)和β-巯基乙醇的DMEM培养基中培养(统称为“培养基A”)。当收到的细胞是冷冻保藏的,需要融化,并且在进行上文描述的培养之前需要建立经过至少3次传代的培养物。
根据引用并入本文的专利号为6,303,151;6,224,912和5,888,497的美国专利的方法在3天之后,ES细胞70-80%融合,经过胰蛋白酶消化之后截留在琼脂糖珠中,并用琼脂糖包被。简而言之,使用起始浓度为大约1.0%的Sigma XII琼脂糖。将100μl该琼脂糖的液体加入34μl细胞悬液中。获得的珠含有2.0×105±1.5×104鼠胚胎干细胞。然后用浓度为大约5.0%的琼脂糖进行第二次琼脂糖包被珠。该珠在没有LIF或可行的STO滋养细胞存在的上述的培养基(培养基B)中培养。
通过标准组织化学和显微检测以及用标准MTT方法,使用从珠子中移出的或者保留在珠子中的细胞在不同的时间点评估随时间变化珠子中细胞的生存能力。
观察到当第一次包被时,截留干细胞增加了它们的新陈代谢活性。之后随着通过凋亡的细胞死亡,活性降低,在大约21天时达到新陈代谢活性的最低点。然而,在这个低点之后,存活的细胞慢慢增殖,并且观察到总新陈代谢活性逐渐地增加直到截留之后的35天以及其以后。这种现象在截留的癌细胞中也平行的观察到。
在形态学上,在珠子的内层琼脂糖中由癌细胞形成的克隆以及由干细胞形成的克隆之间具有显著的不同。尽管两种类型的克隆均是卵形的,由癌细胞形成的那些克隆的特征是较外区域的具有活力的细胞(通常厚度上为两到三个细胞)及中央部的亲曙红(eosiniphilic)细胞碎片区域。另一方面,由干细胞形成的克隆完全是具有活力的细胞并且没有细胞碎片组成的中心区域。
实施例2
在这些实验中,检测了干细胞对其它干细胞增殖的抑制作用。
使用上文讨论的MTT方法检测了十周时间的含有干细胞(SCC-PSA1细胞)的琼脂糖/琼脂糖珠子的生存能力,并且在实施例1中讨论的培养基B中培养琼脂糖/琼脂糖珠子6天。6天之后,截留干细胞适应了培养基。因此称为干细胞适合的培养基(SCM)。
这样6天之后,将SCM转移到含有新鲜SCC-PSA1细胞的六孔板上。这些板每个含有9×105STO滋养层细胞,其由1.5×104SCC-PSA1细胞覆盖。使用丝裂霉素C处理STO细胞,以防止增殖。有三个对照,即含有培养基B(非适合培养基)的孔,以及三个含有SCM的孔。
三天之后,用胰酶消化所有孔中的内含物,并使用标准的方法对总细胞计数。调整粗计数以表明有9×105滋养层细胞。下面是结果:
检测项目 | 平均总细胞 /孔 | 标准偏差 | 减去STO后 的细胞 | 抑制百分比 (SCC细胞) |
对照培养基 | 1.43×106 | ±9.9×104 | 5.27×105 | |
SCM(w/SCC) | 1.19×106 | ±3.6×104 | 2.90×105 | 44.9% |
实施了一个相似的实验,结果如下:
检测项目 | 平均总细胞 /孔 | 标准偏差 | 减去STO后 的细胞 | 抑制百分比 (SCC细胞) |
对照培养基 | 3.09×106 | ±1.7×105 | 1.41×106 | |
SCM(w/SCC) | 2.36×106 | ±9.5×104 | 6.88×105 | 51.4% |
而且,该作用不是细胞系特异的,正如下面结果所表明的,其中将ES-D3细胞加入培养基:
检测项目 | 平均总细 胞/孔 | 标准偏差 | 减去STO后 的细胞 | 抑制百分比 (ES-D3细 胞) |
对照培养基 | 1.27×106 | ±1.1×105 | 3.67×105 | |
SCM(w/SCC) | 1.14×106 | ±7.6×104 | 2.37×105 | 35.5% |
实施例3
实施例2显示干细胞的抑制增殖的作用不是细胞系特异的。在这里描述的实验中,检测截留干细胞抑制癌细胞增殖的能力。
在这些实验中,使用RENCA肿瘤细胞。每孔接种总量为15000个肿瘤细胞。使用如上文描述的SCM(适合SCC-PSA1或者适合ES-D3),以及上文还描述的对照培养基(培养基B)。
关于SCM,适应需要经过5天以上的时间。检测持续32周以上。通过使用100%甲醇固定细胞,随后用中性红染色,SDS裂解,以及使用分光光度计扫描以检测在细胞裂解物中的与每孔中细胞数成比例的中性红的量,来检测RENCA细胞的抑制。
在下述两个表中总结了结果,该表分别代表了ES-D3和SCC-PSA1干细胞的工作。1-3周的结果与实施例1中的论述的结果相关,即,在第21天时,截留干细胞的死亡达到低点,随后开始再生。
周数 | 1 | 3 | 12 | 16 | 20 | 24 | 28 | 32 |
由SCM(w/ES-D3) 产生的RENCA细 胞抑制百分比 | -2.1 % | -8.8 % | 39.0 % | 24.4 % | 25.0 % | 20.9 % | 34.9 % | 31.5 % |
周数 | 1 | 3 | 9 | 12 | 16 | 20 | 24 | 28 | 32 |
由SCM(w/SCC-PSAl) 产生的RENCA细胞抑 制百分比 | -10. 0% | 8.9 % | 21.0 % | 40.4 % | 32.8 % | 22.5 % | 36.6 9% | 38 % | 35.1 % |
实施例4
在前述的实验中,检测并证明了截留干细胞抑制干细胞和癌细胞增殖的能力。设计接下来的实验以确定是否截留的癌细胞能够抑制干细胞的增殖。
用如上文所述的相同的方法对干细胞铺盘并培养。根据专利号为6,303,151;6,224,912和5,888,497的美国专利所描述的制备含有RENCA细胞的珠子,并将其在培养基B中培养5天以使其适应。然后将此RENCA适合的培养基(RCM)加入到铺盘的干细胞,3天之后对干细胞计数。下面的结果分别显示了对于ES-D3细胞和SCC-PSA1细 胞的数据。
检测项目 | 平均总细胞/ 孔 | 标准偏差 | 减去STO后 的细胞 | 抑制百分比 (ES-D3细 胞) |
对照培养基 | 1.69×106 | ±1.15×104 | 7.93×105 | |
RCM | 1.42×106 | ±8.74104 | 5.23×105 | 34.0% |
检测项目 | 平均总细胞/ 孔 | 标准偏差 | 减去STO 后的细胞 | 抑制百分比 (SCC-PSA1 细胞) |
对照培养基 | 1.25×106 | ±8.08×104 | 3.47×105 | |
RCM | 1.05×106 | ±4.04×104 | 1.47×105 | 57.7% |
这些结果显示截留癌细胞确实抑制干细胞的增殖。
实施例5
干细胞研究的一个问题是根据其本性,干细胞将分化的事实。由于很难确保干细胞,防止其在第一步分化,因此期望可以获得一种方法,通过该方法可以使干细胞在其未分化状态保持尽可能长的时间。
为了这个目的,如上文实施例1描述的将干细胞截留。获得的构造物储存在上文描述的培养基B中,并且在超过两年的时间里进行检测。
在这两年的时间里,从截留结构物(structure)中释放出干细胞并用标准的条件进行培养(包括STO共培养以及LIF介质添加剂)。在所有情况中,释放的细胞确立了常规的干细胞单层,其以非分化的方式增殖,但却保留了自发的分化能力。这表明在缺乏常规需要的分化抑制剂(例如STO和LIF)的情况下,截留的干细胞能够在超过两年的时间里维持未分化的表型。
尽管如此,如果细胞在一个短暂时间之后没有接受需要的物质时,在细胞开始分化。
前述实施例描述了本发明,其包括,和其他物质一起,可以用于制备抑制细胞,例如,但不局限于癌细胞和干细胞增殖的物质的组合 物。这些组合物包括截留在选择性的可渗透材料中的干细胞,例如胚胎干细胞,以形成限制截留细胞增殖的结构物。作为被限制的结果,该细胞生成大量的出乎意料的抑制其它细胞增殖的物质。相对于可比较的非限制细胞,限制细胞产生更多的物质。
用于形成本发明结构物所使用的材料可以包括任何生物适合的限制干细胞生长的物质,因此诱导他们生成更大量的细胞增殖生长抑制材料。该结构物具有合适的孔径尺寸,以便上述物质能够扩散到外部环境中,并且以便其能够防止来自宿主免疫系统的产物或细胞进入结构物从而防止发生细胞排斥或者其它的削弱它们存活和继续生成期望物质的能力。用于形成结构物的材料将也能够维持细胞在体外和体内的生存能力(抑制增殖,但存活),优选通过提供加入适当的营养物,除去细胞的废物以及适当的物理化学的结构物内环境而维持长达几年的时间。获得的结构物提供了适合对干细胞以及它们多种分化、转录和核因子进一步研究的环境。由此获得的结果可以用于指导其它干细胞所期望的分化。用于制备结构物的材料优选在植入体内时具有好的耐性(tolerate),最优选在植入宿主的整个期间具有耐性。
可以使用的材料以及材料组合的非限制性列表包括藻酸盐-聚-(L-赖氨酸);藻酸盐-聚-(L-赖氨酸)-藻酸盐;藻酸盐-聚-(L-赖氨酸)-聚乙烯亚胺;壳聚糖-藻酸盐;聚羟基乙烷基-异丁烯酸盐-甲基异丁烯酸盐;羰基甲基纤维素;K-卡拉胶(carragenan);壳聚糖;琼脂糖-聚醚砜-己二-methirine-溴化物(聚凝胺polybrene);乙烷基-纤维素;硅胶及其组合。
含有物质组合物的结构物可以具有多种形态,例如珠形,球形,圆柱形,胶囊,片形或任何适合植入受试者,和/或在体外环境培养的形态。结构物的大小根据其最终用途可以改变,并且对于本领域技术人员是显而易见的。
本发明的结构物是选择性透过的,以便营养物可以进入结构物,以及增殖抑制物质以及细胞废物可以离开结构物。对于体内使用,优选结构物防止将引起细胞排斥,或者其它的削弱细胞生成增殖抑制物质能力的宿主免疫系统的产物或细胞进入结构物。
这里使用的“截留”指细胞包含在一个结构物中,该结构物防止它们逃离到围绕结构物的体外或体内环境中。尽管不能从其中逃离,细胞仍位于一个即允许诸如水、营养物等等分子进入,又允许细胞生成的废物和产物分子离开的结构物中。含有细胞的结构物因此维持细胞长期延续的生存/存活。另外,其还可以依赖于结构物/材料的特性而使得其中所包含的细胞的行为发生改变,该行为包括但不限于,例如增殖,分化的状态和/或表型的表达。通过抑制分化,事实上获得了一个用于维持干细胞为干细胞的存储装置。示例性的但不是排他的截留细胞的方法包括把它们包入胶囊,把它们围起来,把它们封起来或者其它的用某些可渗透的材料将它们从各个面包围起来。通过截留,截留干细胞的增殖被抑制。而且,存在至少部分被截留的群体也不再进行分化的情况。
本发明的另一个方面包括有利于抑制细胞增殖的组合物。在合适的培养基中培养的上文描述的被限制的细胞生成该组合物,随后回收得到的适合的培养基。然后从适合的培养基中形成浓缩物。
本发明不局限于任何特别类型的干细胞种类;根据本发明,可以使用任何类型的干细胞。可以使用的细胞类型的例子是人或鼠干细胞,以及来自于其它物种,特别是哺乳动物物种的干细胞。特别优选胚胎干细胞,但是来自于各种器官和/或器官系统的干细胞也可以使用。
本发明另一个将被清楚公开的方面是用于治疗遭受细胞增殖紊乱疾病个体的方法,该增殖紊乱疾病例如多囊肾疾病、肥大组织反应(hypertrophic tissue reaction)(包括疤痕形成),自身免疫疾病、淋巴-增殖紊乱疾病、真性红细胞增多以及良性和恶性细胞瘤形成。当用于治疗时,如下文详述,限定在结构物中的细胞类型,尽管可以是引起个体所遭受的细胞紊乱疾病的相同类型,但是没有必要是相同的类型。一个这样的方法包括将至少一个足够引起受试者细胞增殖抑制的量的本发明的结构物插入受试者。尽管可以应用于其它动物,例如家畜、农场动物或其它任何动物,但优选受试者是人类。
在治疗多种细胞增殖紊乱疾病的过程中,本发明的组合物可以用作主要的治疗,也可以作为辅助治疗与其它治疗联合使用。例如,在诸如癌症的瘤形成疾病治疗中,可以将本文描述的组合物和方法,与放疗、化疗或使用其它诸如细胞因子、反义分子、甾类激素、基因治 疗等类似的生物活性材料联合使用而治疗患者。另外,本发明的组合物和方法可以与外科手术联合使用而治疗诸如癌症的紊乱疾病,例如,在切除肿瘤之后,通过植入该结构物而防止肿瘤的再生和转移。对于存在于不宜做手术状态的癌症,可以用本发明的抗增殖的组合物进行治疗,使其具有可手术性。可以使用该方法治疗对于正常的器官系统的功能所不需要或不期望的额外的,却又不是瘤形成(neoplastic)的细胞增殖,例如真性红细胞增多或多囊肾疾病的细胞增殖。过度增殖紊乱疾病,例如真性红细胞增多和多囊肾疾病,包含表现为过度增殖,但产生其它正常细胞(即非瘤性或转移的)的细胞。也可以使用这些方法对导致相对正常器官功能不需要或不期望的大量细胞的疾病进行治疗。另外,表现为过度增殖的疾病、例如肥大疤痕的正常细胞也可以使用此方法治疗。在这种情况中,正常细胞,即纤维原细胞,超过伤口愈合需要地增殖,但不象瘤形成那样,其没有进一步的,进行的无节制的增殖。以这种现象为特征的疾病对于本领域技术人员是熟知的,并且不必在这里列举。
可以将本发明的组合物用于预防面临发展为细胞增殖紊乱危险的个体,表现出具有个体风险因素的个体,一般紊乱疾病的家族史的个体,特殊类型疾病家族史(例如乳腺癌)的个体,以及暴露于职业的或其它有问题的材料的个体。例如对于预防癌症,一旦鉴定出一个或多个风险因素,则将有效预防量的本发明的结构物给药给个体。
如上文实施例显示的,抗增殖作用既不受使用的细胞类型的限制,也不受干细胞来源的物种的限制。因此,可以将含有第一种类型的干细胞的结构物给药于不同物种的受试者。例如,可以将鼠干细胞截留在本发明的结构物中,然后给药于人。当然,结构物可以含有与被治疗物同种的干细胞。而且进一步,干细胞可以来自于被治疗的个体,被截留和限制,接着给药于相同的个体。
制备本发明结构物的方法也是本发明的一部分。
对于本领域技术人员而言,本发明的其它方面是显而易见的,而且不需要在这里列出来。
本说明书中使用的术语和措辞是为了说明而不是为了限制,使用这些术语和措辞没有排除任何具有本说明书中所显示和说明的特征或 其部分特征的等价物的意思,在本发明的范围内,各种各样可能的修改也是本发明所认可的。
Claims (23)
1.一种抑制非截留人细胞群的增殖的方法,其包括在存在组合物的条件下培养所述细胞群,所述的组合物含有截留在琼脂糖中的人或鼠干细胞样品,其中所述干细胞不是人类胚胎干细胞,其中所述干细胞样品的截留抑制了非截留细胞群的增殖。
2.根据权利要求1的方法,其中所述的细胞群是干细胞群,该干细胞群不是人类胚胎干细胞群。
3.根据权利要求1的方法,其中所述的细胞群来自于不同于截留在所述组合物中的细胞的物种来源的物种。
4.根据权利要求1的方法,其中所述的细胞群来源于与截留在所述组合物中的细胞的相同物种。
5.根据权利要求1的方法,其中所述的细胞群是癌细胞群。
6.根据权利要求1的方法,其中所述的细胞群是过度增殖的细胞群。
7.一种用于制备抑制受试者中细胞群增殖的药物的组合物的用途,所述的组合物含有截留在琼脂糖中的干细胞样品,其中所述干细胞不是人类胚胎干细胞,其中所述干细胞样品的截留抑制了受试者中细胞群的增殖。
8.根据权利要求7的用途,其中所述的细胞群是干细胞群,该干细胞群不是人类胚胎干细胞群。
9.根据权利要求7的用途,其中所述的细胞群是瘤形成细胞。
10.根据权利要求7的用途,其中所述的细胞群是过度增殖的细胞群。
11.根据权利要求7的用途,其中所述截留在琼脂糖中的干细胞来自于不同于所述受试者的物种。
12.根据权利要求7的用途,其中所述截留在琼脂糖中的干细胞来自于与所述受试者相同的物种。
13.根据权利要求12的用途,其中所述截留在琼脂糖中的干细胞是所述受试者自体的细胞。
14.根据权利要求7的用途,其中所述的受试者是人。
15.根据权利要求12的用途,其中所述的受试者是人。
16.一种抑制干细胞群分化的方法,该干细胞不是人类胚胎干细胞,其包括将所述干细胞截留在琼脂糖中,其中所述干细胞群保持在未分化状态。
17.根据权利要求16的方法,其中所述的琼脂糖用琼脂糖包被。
18.根据权利要求16的方法,其中所述的干细胞是鼠干细胞。
19.根据权利要求16的方法,其中所述的干细胞是胚胎干细胞。
20.根据权利要求16的方法,其中所述的干细胞被截留在琼脂糖和胶原的混合物或琼脂糖和明胶的混合物中。
21.根据权利要求17的方法,其中在从所述的用琼脂糖包被的琼脂糖中释放之前所述截留干细胞群储存超过两年。
22.根据权利要求1的方法,其中所述的琼脂糖用琼脂糖包被。
23.根据权利要求7的用途,其中所述的琼脂糖用琼脂糖包被。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/655,275 US20050053586A1 (en) | 2003-09-04 | 2003-09-04 | Entrapped stem cells and uses thereof |
US10/655,275 | 2003-09-04 | ||
PCT/US2004/025713 WO2005026320A2 (en) | 2003-09-04 | 2004-08-09 | Entrapped stem cells and uses thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101415817A CN101415817A (zh) | 2009-04-22 |
CN101415817B true CN101415817B (zh) | 2014-08-06 |
Family
ID=34226098
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN200480023971.2A Active CN101415817B (zh) | 2003-09-04 | 2004-08-09 | 截留干细胞及其使用 |
Country Status (17)
Country | Link |
---|---|
US (4) | US20050053586A1 (zh) |
EP (1) | EP1660633B9 (zh) |
JP (1) | JP5069466B2 (zh) |
KR (1) | KR101294417B1 (zh) |
CN (1) | CN101415817B (zh) |
AU (1) | AU2004272987C1 (zh) |
CA (1) | CA2537861C (zh) |
DK (1) | DK1660633T3 (zh) |
ES (1) | ES2537755T3 (zh) |
HK (1) | HK1126815A1 (zh) |
IL (1) | IL173342A (zh) |
NO (1) | NO338248B1 (zh) |
NZ (2) | NZ545542A (zh) |
PL (1) | PL1660633T3 (zh) |
PT (1) | PT1660633E (zh) |
RU (1) | RU2346040C2 (zh) |
WO (1) | WO2005026320A2 (zh) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SG131016A1 (en) * | 2005-09-19 | 2007-04-26 | Millipore Corp | Asymmetric porous adsorptive bead |
AU2008266019A1 (en) * | 2007-06-13 | 2008-12-24 | Fmc Corporation | Peptide linked cell matrix materials for stem cells and methods of using the same |
CA2763377A1 (en) * | 2009-05-27 | 2010-12-02 | Bayer Materialscience Ag | Method for producing a coated cell culture carrier |
ES2534374T3 (es) * | 2010-11-23 | 2015-04-22 | The Rogosin Institute, Inc. | Método para aislar una célula cancerosa resistente a agentes quimioterapéuticos con propiedades de célula madre |
EP2688397B1 (en) | 2011-03-21 | 2016-07-20 | University of Reading | Transport of cells in alginate hydrogels |
PL2809782T3 (pl) | 2012-01-31 | 2018-04-30 | The Rogosin Institute, Inc. | Ulepszony sposób wytwarzania makroperełek |
Family Cites Families (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US38027A (en) | 1863-03-31 | Improved method of affixing tubes in steam-condensers | ||
US4409331A (en) | 1979-03-28 | 1983-10-11 | Damon Corporation | Preparation of substances with encapsulated cells |
US4352883A (en) | 1979-03-28 | 1982-10-05 | Damon Corporation | Encapsulation of biological material |
DE3032931C2 (de) | 1980-09-02 | 1982-07-29 | Robert Bürkle GmbH & Co, 7290 Freudenstadt | Verfahren und Anordnung zur Herstellung von Mehrschicht-Leiterplatten |
SE441009B (sv) | 1982-03-08 | 1985-09-02 | Kjell Nilsson | Sett att immobilisera levande biomaterial i perlformiga polymerer |
US4798786A (en) | 1982-05-06 | 1989-01-17 | Stolle Research And Development Corporation | Living cells encapsulated in crosslinked protein |
CA1196862A (en) | 1983-06-01 | 1985-11-19 | Anthony M.F. Sun | Microencapsulation of living tissue and cells |
US4663286A (en) | 1984-02-13 | 1987-05-05 | Damon Biotech, Inc. | Encapsulation of materials |
US4997443A (en) | 1985-08-26 | 1991-03-05 | Hana Biologics, Inc. | Transplantable artificial tissue and process |
US4902295A (en) | 1985-08-26 | 1990-02-20 | Hana Biologics, Inc. | Transplantable artificial tissue |
SE8604684L (sv) | 1986-11-03 | 1988-05-04 | Excorim Kommanditbolag | Sett att belegga fasta partiklar med en hydrofil gel samt genom settet belagda partiklar |
US5053332A (en) | 1989-07-24 | 1991-10-01 | Cook Richard B | Agarose beads, preferably incorporating biological materials |
US5227298A (en) | 1990-08-17 | 1993-07-13 | The Trustees Of Columbia University In The City Of New York | Method for microencapuslation of cells or tissue |
ATE275194T1 (de) | 1994-01-13 | 2004-09-15 | Rogosin Inst | Makroeingekapselte sekretorische zellen |
US5888497A (en) | 1996-04-03 | 1999-03-30 | The Rogosin Institute | Agarose coated agarose beads containing cancer cells that produce material which suppresses cancer cell proliferation |
US6303151B1 (en) * | 1996-04-03 | 2001-10-16 | The Rogosin Institute | Cancer-cell proliferation-suppressing material produced by cancer cells restricted by entrapment |
US6224912B1 (en) * | 1996-04-03 | 2001-05-01 | The Rogo Institute | Cancer-cell proliferation-suppressing material produced by cancer cells restricted by entrapment |
ATE419333T1 (de) * | 2001-02-06 | 2009-01-15 | Massachusetts Inst Technology | Peptidgerüstverkapselung von gewebszellen und verwendungen davon |
CA2351156A1 (en) * | 2001-07-04 | 2003-01-04 | Peter W. Zandstra | A bioprocess for the generation of pluripotent cell derived cells and tissues |
JP2004248505A (ja) * | 2001-09-21 | 2004-09-09 | Norio Nakatsuji | 移植抗原の一部または全てを欠除したes細胞由来の未分化な体細胞融合細胞およびその製造 |
US20050130144A1 (en) * | 2001-09-21 | 2005-06-16 | Norio Nakatsuji | Method of screening reprogramming factor, reprogramming factor screened by the method, method of using the reprogramming factor, method of differentiating undifferentiated fused cells and method of constructing cell, tissues and organs |
JP4317337B2 (ja) * | 2001-10-16 | 2009-08-19 | 株式会社リプロセル | 細胞株継代用酵素溶液、および、それを用いた霊長類胚性幹細胞の培養増殖方法 |
US7101546B2 (en) * | 2001-12-21 | 2006-09-05 | Amcyte, Inc. | In situ maturation of cultured pancreatic stem cells having a specified, intermediate stage of development |
EP1726640B1 (en) * | 2004-03-04 | 2016-01-13 | Sumitomo Dainippon Pharma Co., Ltd. | Rat embryonic stem cell |
-
2003
- 2003-09-04 US US10/655,275 patent/US20050053586A1/en not_active Abandoned
-
2004
- 2004-08-09 PT PT47805353T patent/PT1660633E/pt unknown
- 2004-08-09 CN CN200480023971.2A patent/CN101415817B/zh active Active
- 2004-08-09 AU AU2004272987A patent/AU2004272987C1/en not_active Ceased
- 2004-08-09 PL PL04780535T patent/PL1660633T3/pl unknown
- 2004-08-09 JP JP2006525338A patent/JP5069466B2/ja not_active Expired - Fee Related
- 2004-08-09 EP EP20040780535 patent/EP1660633B9/en active Active
- 2004-08-09 WO PCT/US2004/025713 patent/WO2005026320A2/en active Application Filing
- 2004-08-09 NZ NZ545542A patent/NZ545542A/en not_active IP Right Cessation
- 2004-08-09 DK DK04780535.3T patent/DK1660633T3/en active
- 2004-08-09 RU RU2006110637/13A patent/RU2346040C2/ru active
- 2004-08-09 CA CA2537861A patent/CA2537861C/en active Active
- 2004-08-09 ES ES04780535.3T patent/ES2537755T3/es active Active
- 2004-08-09 KR KR1020067003719A patent/KR101294417B1/ko active IP Right Grant
- 2004-08-09 NZ NZ577865A patent/NZ577865A/en not_active IP Right Cessation
-
2006
- 2006-01-24 IL IL173342A patent/IL173342A/en active IP Right Grant
- 2006-03-31 NO NO20061478A patent/NO338248B1/no unknown
- 2006-06-05 US US11/447,405 patent/US20060216278A1/en not_active Abandoned
-
2007
- 2007-08-10 US US11/891,526 patent/US7838291B2/en active Active
-
2009
- 2009-07-02 HK HK09105911A patent/HK1126815A1/zh not_active IP Right Cessation
-
2011
- 2011-06-09 US US13/156,659 patent/US20110275155A1/en not_active Abandoned
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Maki et al. | Treatment of diabetes by xenogeneic islets without immunosuppression: use of a vascularized bioartificial pancreas | |
RU2268735C1 (ru) | Композиции подвергнутых рестрикции клеток, способных к быстрому росту, которые продуцируют вещества, подавляющие пролиферацию клеток, и их применение | |
Conconi et al. | Homologous muscle acellular matrix seeded with autologous myoblasts as a tissue-engineering approach to abdominal wall-defect repair | |
KR20050055760A (ko) | 질병 치료를 위한 캡슐화 생물학적 물질의 이식 | |
CN101415817B (zh) | 截留干细胞及其使用 | |
EP2878197B1 (en) | Tissue preservation solution and tissue preservation method | |
Liu et al. | Porcine urinary bladder matrix-polypropylene mesh: a novel scaffold material reduces immunorejection in rat pelvic surgery | |
US7297331B2 (en) | Beads containing restricted cancer cells producing material suppressing cancer cell proliferation | |
Kulikov et al. | Effects of allogenic fetal pancreatic tissue transplantation on regeneration of islet cells in recipient rats with alloxan-induced diabetes mellitus. | |
Chowdhury | Stem cell in cancer disease cure vs cause | |
AU2007203602B2 (en) | Entrapped stem cells and uses thereof | |
US20080254090A1 (en) | Porcine Islets Cultured With Porcine Sertoli Cells For Xenotransplantation | |
KR102112267B1 (ko) | 환자 유래 켈로이드 이종 이식 동물 모델 | |
Karbek et al. | The Effects of Cord Blood Serum on Survival of Rat Pancreatic Islets during | |
MXPA06002579A (en) | Entrapped stem cells and uses thereof | |
Ibrasheva | STEM CELLS AND SOCIETY | |
House et al. | Effect of serial transplantation on the growth of neonatal pancreas in the hamster | |
POPESCU et al. | BONE-MARROW STORAGE AND TRANSPLANTATION |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1126815 Country of ref document: HK |
|
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: GR Ref document number: 1126815 Country of ref document: HK |