EP0190337A1 - A process for proliferation of wholly or partially differentiated beta-cellls - Google Patents
A process for proliferation of wholly or partially differentiated beta-celllsInfo
- Publication number
- EP0190337A1 EP0190337A1 EP19850904430 EP85904430A EP0190337A1 EP 0190337 A1 EP0190337 A1 EP 0190337A1 EP 19850904430 EP19850904430 EP 19850904430 EP 85904430 A EP85904430 A EP 85904430A EP 0190337 A1 EP0190337 A1 EP 0190337A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- islets
- cells
- culture medium
- growth hormone
- human
- 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.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 title claims abstract description 16
- 230000035755 proliferation Effects 0.000 title claims abstract description 7
- 210000004027 cell Anatomy 0.000 claims abstract description 22
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 claims abstract description 17
- 108010051696 Growth Hormone Proteins 0.000 claims abstract description 16
- 102000018997 Growth Hormone Human genes 0.000 claims abstract description 16
- 239000000122 growth hormone Substances 0.000 claims abstract description 16
- 210000002966 serum Anatomy 0.000 claims abstract description 13
- 239000000758 substrate Substances 0.000 claims abstract description 7
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 6
- 239000008103 glucose Substances 0.000 claims abstract description 6
- 239000007787 solid Substances 0.000 claims abstract description 6
- 241001465754 Metazoa Species 0.000 claims abstract description 5
- 235000015097 nutrients Nutrition 0.000 claims abstract description 5
- 238000012258 culturing Methods 0.000 claims abstract 2
- 239000002609 medium Substances 0.000 claims description 12
- 239000001963 growth medium Substances 0.000 claims description 8
- 108010067035 Pancrelipase Proteins 0.000 claims description 7
- 229940088597 hormone Drugs 0.000 claims description 5
- 239000005556 hormone Substances 0.000 claims description 5
- 108010000521 Human Growth Hormone Proteins 0.000 claims description 4
- 102000002265 Human Growth Hormone Human genes 0.000 claims description 4
- 239000000854 Human Growth Hormone Substances 0.000 claims description 4
- 210000003754 fetus Anatomy 0.000 claims description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 abstract description 34
- 102000004877 Insulin Human genes 0.000 abstract description 17
- 108090001061 Insulin Proteins 0.000 abstract description 17
- 229940125396 insulin Drugs 0.000 abstract description 17
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 210000000496 pancreas Anatomy 0.000 abstract description 3
- 230000002062 proliferating effect Effects 0.000 abstract description 3
- 238000000151 deposition Methods 0.000 abstract description 2
- 230000007774 longterm Effects 0.000 abstract description 2
- 230000000050 nutritive effect Effects 0.000 abstract 1
- 210000004153 islets of langerhan Anatomy 0.000 description 10
- 239000012980 RPMI-1640 medium Substances 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 230000006820 DNA synthesis Effects 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 102100021809 Chorionic somatomammotropin hormone 1 Human genes 0.000 description 3
- 108010003044 Placental Lactogen Proteins 0.000 description 3
- 239000000381 Placental Lactogen Substances 0.000 description 3
- 108010057464 Prolactin Proteins 0.000 description 3
- 102100024819 Prolactin Human genes 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 229940097325 prolactin Drugs 0.000 description 3
- 102000016911 Deoxyribonucleases Human genes 0.000 description 2
- 108010053770 Deoxyribonucleases Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000007775 late Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000004264 monolayer culture Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 102000001690 Factor VIII Human genes 0.000 description 1
- 108010054218 Factor VIII Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000976075 Homo sapiens Insulin Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 206010000210 abortion Diseases 0.000 description 1
- 231100000176 abortion Toxicity 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 235000015278 beef Nutrition 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 229960000301 factor viii Drugs 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/62—Insulins
-
- 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
- C12N5/0676—Pancreatic 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/30—Hormones
- C12N2501/305—Growth hormone [GH], aka. somatotropin
Definitions
- the present invention relates to a process of the type defined in the introductory portion of claim 1 for pro ⁇ liferation of wholly or partially differentiated beta- cells .
- the type I diabetes ellitus disease is usually accompanied by progressive destruction of the insulin producing so-called beta-cells in the islets of Langerhans.
- Patients suffering from this disease are normally treated with daily injections of insulin re ⁇ covered from the pancreas from animals, such as beef or pig, or produced by engineering.
- this mode of treatment is still incomplete, and complications at the advanced stages of the disease result in a high mortality rate among diabetics.
- a considerably better regulation of the glucose content of the blood may be obtained by transplantation of tissue from pancrease or isolated islets of Langerhans, which is believed to reduce the risk of the mentioned complications considerably.
- this treatment it is required that sufficient amounts of insulin producing tissue are provided
- the number of available human pancrease organs is by and large the same as the number of kidney donors since the pancrease organs are obtained from the same deceased persons.
- Another source is pancrease from fetal tissue from abortions, but this source, too, is limited. There ⁇ fore, the ability of proliferating the insulin producing cells by cell cultivation is very important (ref. 1).
- beta-cell division Even with rat islets of Langerhans, only limited beta-cell division has been observed, which has led to the general assumption that the postnatal division capacity qf the beta-cell is poor, while some neoformation and/or division of beta-cells in vitro seems to occur in the embryonic and very late fetal state (see ref. 4). Only few cases of stimulation of beta-cell division in vitro have been reported, and it has generally been believed that glucose is the most important factor in cell division both in vivo and in vitro (ref. 4).
- the conventional method of cultivating cells is performed by depositing the cells on the surface of a solid substrate, e.g. of a plastics material. Such deposit is promoted by the presence of serum, e.g. 10% fetal calf serum, which is therefore widely used in the cultivation of insulin producing cells (ref. 6). Under these conditions, no effect of growth hormone was observed, either on the DNA synthesis or the insulin production (ref. 7). Increased insulin production is described (ref. 8), and an increased DNA synthesis without an increase in insulin secretion is likewise described (ref. 9 and ref. 10). While considerable, but time-limited stimulation of both insulin production and DNA synthesis has been demonstrated in the intact islets (ref. 5), this has so far not been demonstrated in monolayer cultures.
- serum e.g. 10% fetal calf serum
- the object of the present process is to provide an efficient and rational method of proliferating wholly or partially differentiated beta-cells in large amounts.
- Another object of the invention is to proliferate , cells which produce insulin in considerable amounts and which are useful for implantation in humans.
- a further object of the invention is to produce human insulin.
- the process of the invention which is characterized by the features stated in the characterizing portion of claim 1, is based on the surprising finding that wholly or partially differentiated beta-cells develop strongly with formation of monolayers by cultivation on a solid substrate and in contact with a nutrient medium containing both serum and growth hormone in the stated concentration ranges, and when the nutrient medium is repeatedly exchanged during a cultivation period of preferably several weeks .
- the nutrient medium used in the proliferation of the cells may expediently have a relatively high content of glucose, such as 1/2 - 10 g/1 , preferably 1.5 - 5 g/1, with 2 g/1 as the optimum value.
- the content of human serum is expediently 1/2 - 1% , preferably 1/2 - 3% , with about 2? ⁇ as the optimum value.
- Growth hormone of animal or human origin may be replaced by hormones having similar properties, such as prolactin or placental lactogen.
- the preferred concentration of growth hormone or the hormone having similar properties in the culture medium is 10 to 1000 ng/ml, such as about 100 ng/ l.
- a consider ⁇ able effect may also be obtained, however, at lower con ⁇ centrations, such as down to about 1 ng/ml.
- Larger amounts of growth hormone may also be used, such as up to 1000 ng/ml culture medium or more, but, usually, no consider ⁇ ably improved cell formation is obtained at higher concentrations than 200 ng/ml.
- the process of the invention permits proliferation of insulin producing cells of any type, also in the form of host cells into which one or more other genes which are to be expressed in an.i ⁇ ral or human cells have been intro ⁇ quizzed. Examples of this are cells in which DNA fragments which code for Factor VIII, growth hormone or interferon have been introduced.
- Pancrease from 15 three days old rats is excised, treated with collagenase, and the islets are isolated as described in ref. 5. 1000 islets are placed in culture medium RPMI 1640 containing 10? ⁇ serum from newborn calves, distributed with 100 islets in 5 ml medium in Petri dishes. The dishes stand at 37 °C for 2 days as described in ref. 5. Then the islets are treated with a mixture of EGTA, DNase and trypsin and are aspirated until a cell suspension has been obtained, as described in ref. 11. The cells are suspended in medium RPMI 1640, and 10 cells in 5 ml medium are placed in cell cultivation dishes, as described in ref. 9. The dishes stand for 2 days at 37 °C, and the medium is then changed to RPMI 1640 admixed with 2% normal human serum and 100 ng/ml human growth hormone (Nanormon,
- the dishes stand at 37 °C, and the medium is changed once a week. Insulin is measured by radioimmunoassay , as described in ref. 5.
- the cells proliferate to colonies, and after 5 months the colonies have spread so that they cover almost the entire dish. They are treated with a mixture of EGTA, DNase and trypsin, and the resulting cell suspension is placed in new dishes with the media RPMI 1640 admixed with.2% normal human serum and 100 ng/ml human growth hormone. Again the cells proliferate to colonies and spread in the dish. The insulin production increases again gradually.
- curve I refers to the experiment performed in this example.
- Curve II refers to a comparative example performed in the same manner, except that no growth hormone was added.
- a cell suspension is produced as described in example 1.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Toxicology (AREA)
- Cell Biology (AREA)
- Endocrinology (AREA)
- Microbiology (AREA)
- Diabetes (AREA)
- General Engineering & Computer Science (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK402984A DK402984D0 (da) | 1984-08-23 | 1984-08-23 | Fremgangsmaade til formering af insulin-producerende celler |
| DK4029/84 | 1984-08-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0190337A1 true EP0190337A1 (en) | 1986-08-13 |
Family
ID=8129448
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP19850904430 Withdrawn EP0190337A1 (en) | 1984-08-23 | 1985-08-23 | A process for proliferation of wholly or partially differentiated beta-cellls |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0190337A1 (da) |
| AU (1) | AU4805185A (da) |
| DK (1) | DK402984D0 (da) |
| WO (1) | WO1986001530A1 (da) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK0605428T5 (da) * | 1991-06-24 | 2003-01-06 | Hcell Technology Inc | Hormonsecernerende pancreasceller opretholdt i langtidskultur |
| US5747341A (en) * | 1991-06-24 | 1998-05-05 | Pacific Biomedical Research, Inc. | Culture media having low osmolarity for establishing and maintaining hormone-secreting cells in long-term culture |
| US5821121A (en) * | 1991-06-24 | 1998-10-13 | Pacific Biomedical Research, Inc. | Hormone-secreting cells maintained in long-term culture |
| US6001647A (en) * | 1994-04-28 | 1999-12-14 | Ixion Biotechnology, Inc. | In vitro growth of functional islets of Langerhans and in vivo uses thereof |
| US5834308A (en) * | 1994-04-28 | 1998-11-10 | University Of Florida Research Foundation, Inc. | In vitro growth of functional islets of Langerhans |
| US6703017B1 (en) | 1994-04-28 | 2004-03-09 | Ixion Biotechnology, Inc. | Reversal of insulin-dependent diabetes by islet-producing stem cells, islet progenitor cells and islet-like structures |
| WO2002002750A1 (en) * | 2000-06-30 | 2002-01-10 | Amcyte, Inc. | Culturing pancreatic stem cells having a specified, intermediate stage of development |
| US7202080B2 (en) | 2001-03-29 | 2007-04-10 | Ixion Biotechnology, Inc. | Method for transdifferentiation of non-pancreatic stem cells to the pancreatic differentiation pathway |
| KR20030033638A (ko) * | 2001-10-24 | 2003-05-01 | (주)한국췌도이식연구소 | 인공 췌도 세포 및 이의 용도 |
| DE10313291A1 (de) * | 2003-03-25 | 2004-10-14 | Universität Leipzig | Mediumzusammensetzung für das Tissue engineering vaskularisierter Gewebe und von Blutgefäßen |
| US8735154B2 (en) | 2006-10-30 | 2014-05-27 | The University Of Kansas | Templated islet cells and small islet cell clusters for diabetes treatment |
| WO2013016544A2 (en) | 2011-07-27 | 2013-01-31 | University Of Kansas | Templated islet cells and small islet cell clusters for diabetes treatment |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2726313C3 (de) * | 1977-06-10 | 1980-02-07 | Battelle-Institut E.V., 6000 Frankfurt | Verfahren zur in-vitro-Biosynthese von Hormonen, insbesondere von Insulin |
| DE2757169A1 (de) * | 1977-12-22 | 1979-07-05 | Hoechst Ag | Verfahren zur gewinnung insulin produzierender tierischer zellen |
| JPS5729294A (en) * | 1980-07-30 | 1982-02-17 | Hayashibara Biochem Lab Inc | Preparation of human insulin |
-
1984
- 1984-08-23 DK DK402984A patent/DK402984D0/da unknown
-
1985
- 1985-08-23 AU AU48051/85A patent/AU4805185A/en not_active Abandoned
- 1985-08-23 EP EP19850904430 patent/EP0190337A1/en not_active Withdrawn
- 1985-08-23 WO PCT/DK1985/000083 patent/WO1986001530A1/en not_active Ceased
Non-Patent Citations (1)
| Title |
|---|
| See references of WO8601530A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1986001530A1 (en) | 1986-03-13 |
| AU4805185A (en) | 1986-03-24 |
| DK402984D0 (da) | 1984-08-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE60318920T2 (de) | Induktion von Insulin-produzierenden Zellen | |
| US5888816A (en) | Cell cultures of and cell culturing method for nontransformed pancreatic, thyroid, and parathyroid cells | |
| AU780794B2 (en) | Pancreatic progenitor cells, methods and uses related thereto | |
| Lasfargues et al. | A method for the continuous cultivation of mammary epithelium | |
| US20040132183A1 (en) | Methods and compositions for expanding and differentiating insulin-producing cells | |
| JP2004531262A (ja) | ヒト胚性幹細胞由来インスリン産生細胞 | |
| JPS6237607B2 (da) | ||
| DE69936306T2 (de) | C3a serumfreie klonale zell-linie sowie deren anwendungen | |
| EP0190337A1 (en) | A process for proliferation of wholly or partially differentiated beta-cellls | |
| EP0953633A1 (en) | Cell culturing method and medium for producing proliferated, normal, differentiated human liver cells | |
| US5861278A (en) | HNF3δ compositions | |
| JPH11514877A (ja) | 機能性ランゲルハンス島のインビトロ成長およびそのインビボの使用 | |
| KR101025880B1 (ko) | 성체 줄기세포를 이용한 인슐린 분비세포로의 분화 유도방법 | |
| US6136600A (en) | Method for cultivation of hepatocytes | |
| US5756094A (en) | Methods for stimulating follicular growth | |
| Hayek et al. | Enhancement of pancreatic islet cell monolayer growth by endothelial cell matrix and insulin | |
| SIMPSON et al. | Trypanosoma brucei: Differentiation of in Vitro‐Grown Bloodstream Trypomastigotes into Procyclic Forms 1 | |
| US6008047A (en) | Cell culturing method and medium | |
| KR19990014353A (ko) | 췌도의 대량 배양증식방법 | |
| Sukhikh et al. | Stem cell transplantation for treatment of liver diseases: from biological foundations to clinical experience | |
| Howard et al. | Stimulation of thymidine uptake and cell proliferation in mouse embryo fibroblasts by conditioned medium from mammary cells in culture | |
| US11788062B2 (en) | Functional feline pancreatic cells from adipose tissue | |
| CA2216870C (en) | Compositions and methods for regulating hair growth | |
| US12584110B2 (en) | Functional feline pancreatic cells from adipose tissue | |
| Flatt et al. | Tumour formation and insulin secretion by clonal RINm5F cells following repeated subcutaneous transplantation in NEDH rats |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE FR GB IT LI LU NL SE |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
| 18D | Application deemed to be withdrawn |
Effective date: 19860724 |
|
| RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: NIELSEN, JENS HOIRIIS |